Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

ABSTRACT

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, compositions containing such molecules, and processes of using such molecules and compositions against such pests. These molecules and compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”).

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of, and priority from, U.S.Provisional Patent Application Ser. Nos. 62/286,655 and 62/286,673 bothfiled Jan. 25, 2016, each of which are expressly incorporated byreference herein.

FIELD OF THIS DISCLOSURE

This disclosure relates to the field of molecules having pesticidalutility against pests in Phyla Arthropoda, Mollusca, and Nematoda,processes to produce such molecules, intermediates used in suchprocesses, pesticidal compositions containing such molecules, andprocesses of using such pesticidal compositions against such pests.These pesticidal compositions may be used, for example, as acaricides,insecticides, miticides, molluscicides, and nematicides.

BACKGROUND OF THIS DISCLOSURE

“Many of the most dangerous human diseases are transmitted by insectvectors” (Rivero et al.). “Historically, malaria, dengue, yellow fever,plague, filariasis, louse-borne typhus, trypanosomiasis, leishmaniasis,and other vector borne diseases were responsible for more human diseaseand death in the 17^(th) through the early 20^(th) centuries than allother causes combined” (Gubler). Vector-borne diseases are responsiblefor about 17% of the global parasitic and infectious diseases. Malariaalone causes over 800,000 deaths a year, 85% of which occur in childrenunder five years of age. Each year there are about 50 to about 100million cases of dengue fever. A further 250,000 to 500,000 cases ofdengue hemorrhagic fever occur each year (Matthews). Vector controlplays a critical role in the prevention and control of infectiousdiseases. However, insecticide resistance, including resistance tomultiple insecticides, has arisen in all insect species that are majorvectors of human diseases (Rivero et al.). Recently, more than 550arthropod pest species have developed resistance to at least onepesticide (Whalon et al.).

Each year insects, plant pathogens, and weeds, destroy more than 40% ofall food production. This loss occurs despite the application ofpesticides and the use of a wide array of non-chemical controls, suchas, crop rotations, and biological controls. If just some of this foodcould be saved, it could be used to feed the more than three billionpeople in the world who are malnourished (Pimental).

Plant parasitic nematodes are among the most widespread pests, and arefrequently one of the most insidious and costly. It has been estimatedthat losses attributable to nematodes are from about 9% in developedcountries to about 15% in undeveloped countries. However, in the UnitedStates of America a survey of 35 States on various crops indicatednematode-derived losses of up to 25% (Nicol et al.).

It is noted that gastropods (slugs and snails) are pests of lesseconomic importance than other arthropods or nematodes, but in certainplaces they may reduce yields substantially, severely affecting thequality of harvested products, as well as, transmitting human, animal,and plant diseases. While only a few dozen species of gastropods areserious regional pests, a handful of species are important pests on aworldwide scale. In particular, gastropods affect a wide variety ofagricultural and horticultural crops, such as, arable, pastoral, andfiber crops; vegetables; bush and tree fruits; herbs; and ornamentals(Speiser).

Termites cause damage to all types of private and public structures, aswell as, to agricultural and forestry resources. In 2005, it wasestimated that termites cause over US $50 billion in damage worldwideeach year (Korb).

Consequently, for many reasons, including those mentioned above, thereis an on-going need for the costly (estimated to be about US $256million per pesticide in 2010), time-consuming (on average about 10years per pesticide), and difficult, development of new pesticides(CropLife America).

DeMassey et al. discloses the following structure. For more detail,refer to US 2002/0068838.

CERTAIN REFERENCES CITED IN THIS DISCLOSURE

-   CropLife America, The Cost of New Agrochemical Product Discovery,    Development & Registration, and Research & Development predictions    for the Future, 2010.-   Gubler, D., Resurgent Vector-Borne Diseases as a Global Health    Problem, Emerging Infectious Diseases, Vol. 4, No. 3, p. 442-450,    1998.-   Korb, J., Termites, Current Biology, Vol. 17, No. 23, 2007.-   Matthews, G., Integrated Vector Management: Controlling Vectors of    Malaria and Other Insect Vector Borne Diseases, Ch. 1, p. 1-2011.-   Nicol, J., Turner S.; Coyne, L.; den Nijs, L., Hocksland, L.,    Tahna-Maafi, Z., Current Nematode Threats to World Agriculture,    Genomic and Molecular Genetics of Plant—Nematode Interactions, p.    21-43, 2011).-   Pimental, D., Pest Control in World Agriculture, Agricultural    Sciences—Vol. II, 2009.-   Rivero, A., Vezilier, 3., Weill, M., Read, A., Gandon, S., Insect    Control of Vector-Borne Diseases: When is Insect Resistance a    Problem? Public Library of Science Pathogens, Vol. 6, No. 8, p. 1-9,    2010.-   Speiser, B., Molluscicides, Encyclopedia of Pest Management, Ch.    219, p. 506-508, 2002.-   Whalon, M., Mota-Sanchez, D., Hollingworth, R., Analysis of Global    Pesticide Resistance in Arthropods, Global Pesticide Resistance in    Arthropods, Ch. 1, p. 5-33, 2008.

Definitions Used in this Disclosure

The examples given in these definitions are generally non-exhaustive andmust not be construed as limiting the disclosure. It is understood thata substituent should comply with chemical bonding rules and stericcompatibility constraints in relation to the particular molecule towhich it is attached. These definitions are only to be used for thepurposes of this disclosure.

“Active ingredient” means a material having activity useful incontrolling pests, and/or that is useful in helping other materials havebetter activity in controlling pests, examples of such materialsinclude, but are not limited to, acaricides, algicides, avicides,bactericides, fungicides, herbicides, insecticides, molluscicides,nematicides, rodenticides, virucides, antifeedants, bird repellents,chemosterilants, herbicide safeners, insect attractants, insectrepellents, mammal repellents, mating disrupters, plant activators,plant growth regulators, and synergists. Specific examples of suchmaterials include, but are not limited to, the materials listed inactive ingredient group alpha.

“Active ingredient group alpha” (hereafter “AIGA”) means collectivelythe following materials:

(1) (3-ethoxypropyl)mercury bromide, 1,2-dibromoethane,1,2-dichloroethane, 1,2-dichloropropane, 1,3-dichloropropene, 1-MCP,1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,3-TPA,2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,4,5-T, 2,4,5-TB, 2,4,5-TP,2,4-D, 2,4-DB, 2,4-DEB, 2,4-DEP, 2,4-DES, 2,4-DP, 2,4-MCPA, 2,4-MCPB,2iP, 2-methoxyethylmercury chloride, 2-phenyiphenol, 3,4-DA, 3,4-DB,3,4-DP, 3,6-dichloropicolinic acid, 4-aminopyridine, 4-CPA, 4-CPB,4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate,8-phenylmercurioxyquinoline, abamectin, abamectin-aminomethyl, abscisicacid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor,acetofenate, acetophos, acetoprole, acibenzolar, acifluorfen, aclonifen,ACN, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs,afidopyropen, afoxolaner, alachlor, alanap, alanycarb, albendazole,aldicarb, aldicarb sulfone, aldimorph, aldoxycarb, aldrin, allethrin,allicin, allidochlor, allosamidin, alloxydim, allyl alcohol, allyxycarb,alorac, alpha-cyperrnethrin, alpha-endosulfan, alphamethrin,altretamine, aluminium phosphide, aluminum phosphide, ametoctradin,ametridione, ametryn, ametryne, amibuzin, amicarbazone, amicarthiazol,amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor,aminopyralid, aminotriazole, amiprofos-methyl, amiprophos,amiprophos-methyl, amisuibrom, amiton, amitraz, amitrole, ammoniumsulfamate, amobam, amorphous silica gel, amorphous silicon dioxide,ampropylfos, AMS, anabasine, ancymidol, anilazine, anilofos, anisuron,anthraquinone, antu, apholate, aramite, arprocarb, arsenous oxide,asomate, aspirin, asulam, athidathion, atraton, atrazine, aureofungin,ivermectin B1, AVG, aviglycine, azaconazole, azadirachtin, azafenidin,azamethiphos, azidithion, azimsulfuron, azinphosethyl, azinphos-ethyl,azinphosmethyl, azinphos-methyl, aziprotryn, aziprotryne, azithiram,azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban,barbanate, barium hexafluorosilicate, barium polysulfide, bariumsilicofluoride, barthrin, basic copper carbonate, basic copper chloride,basic copper sulfate, BCPC, beflubutarnid, benalaxyl, benalaxyl-M,benazolin, bencarbazone, benclothiaz, bendaqingbingzhi, bendiocarb,bendioxide, benefin, benfluralin, benfuracarb, benfuresate,benmihuangcaoan, benodanil, benomyl, benoxacor, benoxafos, benquinox,bensulfuron, bensulide, bensultap, bentaluron, bentazon, bentazone,benthiavalicarb, benthiazole, benthiocarb, bentranil, benzadox,benzalkonium chloride, benzamacril, benzamizole, benzamorf, benzenehexachloride, benzfendizone, benzimine, benzipram, benzobicyclon,benzoepin, benzofenap, benzofluor, benzohydroxamic acid, benzomate,benzophosphate, benzothiadiazole, benzovindiflupyr, benzoximate,benzoylprop, benzthiazuron, benzuocaotong, benzyl benzoate,benzyladenine, berberine, beta-cyfluthrin, beta-cypermethrin,bethoxazin, BHC, bialaphos, bicyclopyrone, bifenazate, bifenox,bifenthrin, bifujunzhi, bilanafos, binapacryl, bingqingxiao,bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl,bisazir, bismerthiazol, bismerthiazol-copper, bisphenylmercurymethylenedi(x-naphthalene-y-sulphonate), bispyribac, bistrifluron,bisultap, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeauxmixture, boric acid, boscalid, BPPS, brassinolide, brassinolide-ethyl,brevicornin, brodifacoum, brofenprox, brofenvalerate, broflanilide,brofluthrinate, bromacil, bromadiolone, bromchlophos, bromethalin,bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide,bromociclen, bromocyclen, bromo-DDT, bromofenoxim, bromofos,bromomethane, bromophos, bromophos-ethyl, bromopropylate, bromothalonil,brornoxynil, brompyrazon, bromuconazole, bronopol, BRP, BTH,bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundymixture, busulfan, busulphan, butacarb, butachlor, butafenacil, butam,butamifos, butane-fipronil, butathiofos, butenachior, butene-fipronil,butethrin, buthidazole, buthiobate, buthiuron, butifos, butocarboxim,butonate, butopyronoxyl, butoxycarboxim, butralin, butrizol, butroxydim,buturon, butylamine, butylate, butylchlorophos, butylene-fipronil,cacodylic acid, cadusafos, cafenstrole, calciferol, calcium arsenate,calcium chlorate, calcium cyanamide, calcium cyanide, calciumpolysulfide, calvinphos, cambendichior, camphechior, camphor, captafol,captan, carbam, carbamorph, carbanolate, carbaril, carbaryl, carbasulam,carbathion, carbendazim, carbendazol, carbetamide, carbofenotion,carbofuran, carbon disulfide, carbon tetrachloride, carbonyl sulfide,carbophenothion, carbophos, carbosulfan, carboxazole, carboxide,carboxin, carfentrazone, carpropamid, cartap, carvacrol, carvone, CAVP,CDAA, CDEA, CDEC, cellocidin, CEPC, ceralure, cerenox, cevadilla,Cheshunt mixture, chinaiphos, chinalphos-methyl, chinomethionat,chinomethionate, chiralaxyl, chitosan, chlobenthiazone, chlomethoxyfen,chloralose, chloramben, chloramine phosphorus, chloramphenicol,chloraniformethan, chloranil, chloranocryl, chlorantraniliprole,chlorazifop, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen,chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform,chlorempenthrin, chioretazate, chlorethephon, chiorethoxyfos,chloreturon, chlorfenac, chiorfenapyr, chlorfenazole, chlorfenethol,chlorfenidim, chiorfenprop, chiorfenson, chlorfensulphide,chlorfenvinphos, chlorfenvinphos-methyl, chlorfluazuron, chlorflurazole,chlorflurecol, chiorfiuren, chlorflu enol, chloridazon, chlorimuron,chlorinate, chlor-IPC, chlormephos, chlormequat, chlormesulone,chlormethoxynil, chlornidine, chlornitrofen, chloroacetic acid,chlorobenzilate, chlorodinitronaphthalenes, chlorofenizon, chloroform,chloromebuform, chloromethiuron, chioroneb, chlorophacinone, chiorophos,chloropicrin, chloropon, chloropropylate, chlorothalonil, chiorotoluron,chloroxifenidim, chloroxuron, chloroxynil, chlorphonium, chiorphoxim,chiorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal,chlorthiamid, chiorthiophos, chlortoluron, chlozolinate, chitosan,cholecalciferol, choline chloride, chromafenozide, cicloheximide,cimectacarb, cimetacarb, cinerin I, cinerin II, cinerins, cinidon-ethyl,cinmethylin, cinosulfuron, cintofen, ciobutide, cisanilide, cismethrin,clacyfos, clefoxydim, clenpirin, clenpyrin, clethodim, climbazole,cliodinate, clodinafop, cloethocarb, clofencet, clofenotane,clofentezine, clofenvinfos, clofibric acid, clofop, clomazone,clomeprop, clonitralid, cloprop, cloproxydim, clopyralid, cloquintocet,cloransulam, closantel, clothianidin, clotrimazole, cloxyfonac,cloxylacon, clozylacon, CMA, CMMP, CMP, CMU, codlelure, colecalciferol,colophonate, copper 8-quinolinolate, copper acetate, copperacetoarsenite, copper arsenate, copper carbonate basic, copperhydroxide, copper naphthenate, copper oleate, copper oxychloride, coppersilicate, copper sulfate, copper sulfate basic, copper zinc chromate,coumachlor, coumafene, coumafos, coumafuryl, coumaphos, coumatetralyl,coumethoxystrobin, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC,credazine, cresol, cresylic acid, crimidine, crotamiton, crotoxyfos,crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyleron,cumyluron, cuprobam, cuprous oxide, curcumenol, CVMP, cyanamide,cyanatryn, cyanazine, cyanofenphos, cyanogen, cyanophos, cyanthoate,cyantraniliprole, cyanuric acid, cyazofamid, cybutryne, cyclafuramid,cyclanilide, cyclaniliprole, cyclethrin, cycloate, cycloheximide,cycloprate, cycloprothrin, cyclopyrimorate, cyclosulfamuron,cycloxydirn, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen,cyfluthrin, cyhalofop, cyhalothrin, cyhexatin, cymiazole, cymoxanil,cyometrinil, cypendazole, cypermethrin, cyperquat, cyphenothrin,cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid,cyprosulfamide, cyromazine, cythioate, cytrex, daimuron, dalapon,daminozide, dayoutong, dazomet, DBCP, d-camphor, DCB, DCIP, DCPA, DCPTA,DCU, DDD, DDPP, DDT, DDVP, debacarb, decafentin, decamethrin,decarbofuran, deet, dehydroacetic acid, deiquat, delachlor, delnav,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methyl sulphone, demeton-S-methylsulphon,DEP, depallethrine, derris, desmedipham, desmetryn, desmetryne,d-fanshiluquebingjuzhi, diafenthiuron, dialifor, dialifos, diallate,diamidafos, dianat, diatomaceous earth, diatomite, diazinon, dibrom,dibutyl phthalate, dibutyl succinate, dicamba, dicapthon, dichlobenil,dichiofenthion, dichlofluanid, dichione, dichloralurea, dichlorbenzuron,dichlorfenidim, dichlorflurecol, dichlorflurenol, dichiormate,dichiormid, dichloromethane, dicloromezotiaz, dichlorophen, dichlorprop,dichlorprop-P, dichlorvos, dichlozolin, dichlozoline, diclobutrazol,diclocymet, diclofop, diclomezine, dicloran, diclosulam, dicofol,dicophane, dicoumarol, dicresyl, dicrotophos, dicryl, dicumarol,dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethatyl,diethion, diéthion, diethofencarb, dietholate, diéthon, diethylpyrocarbonate, diethyltoluamide, difenacoum, difenoconazole,difenopenten, difenoxuron, difenzoquat, difethialone, diflovidazin,diflubenzuron, diflufenican, diflufenicanil, diflufenzopyr,diflumetorim, dikegulac, dilor, dimatif, dimefluthrin, dimefox,dimefuron, dimehypo, dimepiperate, dimetachione, dimetan, dimethacarb,dimethachlone, dimethachlor, dimethametryn, dimethenamid,dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph,dimethrin, dimethyl carbate, dimethyl disulfide, dimethyl phthalate,dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin,dimpylate, dimuron, dinex, dingjunezuo, diniconazole, diniconazole-M,dinitramine, dinitrophenols, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb,dinosulfon, dinotefuran, dinoterb, dinoterbon, diofenolan,dioxabenzofos, dioxacarb, dioxathion, dioxation, diphacin, diphacinone,diphenadione, diphenamid, diphenamide, diphenyl sulfone, diphenylamine,diphenylsulphide, diprogulic acid, dipropalin, dipropetryn, dipterex,dipymetitrone, dipyrithione, diquat, disodium tetraborate, disosultap,disparlure, disugran, disul, disulfiram, disulfoton, ditalimfos,dithianon, dithicrofos, dithioether, dithiométon, dithiopyr, diuron,dixanthogen, d-limonene, DMDS, DMPA, DNOC, dodemorph, dodicin, dodine,dofenapyn, doguadine, dominicalure, doramectin, DPC, drazoxolon, DSMA,d-trans-allethrin, d-trans-resmethrin, dufulin, dymron, EBEP, EBP,ebufos, ecdysterone, echlomezol, EDB, EDC, EDDP, edifenphos, eglinazine,emamectin, EMPC, empenthrin, enadenine, endosulfan, endothal, endothall,endothion, endrin, enestroburin, enilconazole, enoxastrobin,ephirsulfonate, EPN, epocholeone, epofenonane, epoxiconazole,eprinornectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan,esdépalléthrine, esfenvalerate, ESP, esprocarb, etacelasil, etaconazole,etaphos, etem, ethaboxarn, ethachlor, ethalfiuralin, ethametsulfuron,ethaprochior, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion,ethiozin, ethiprole, ethirimol, ethoate-methyl, ethobenzanid,ethofumesate, ethohexadiol, ethoprop, ethoprophos, ethoxyfen,ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethylpyrophosphate, ethylan, ethyl-DDD, ethylene, ethylene dibromide,ethylene dichloride, ethylene oxide, ethylicin, ethylmercury2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylrnercurybromide, ethylmercury chloride, ethylmercury phosphate, etinofen, ETM,etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos,étrimphos, eugenol, EXD, famoxadone, famphur, fenac, fenamidone,fenaminosulf, fenaminstrobin, fenamiphos, fenapanil, fenarimol,fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide,fenchlorazole, fenchiorphos, fenclofos, fenclorim, fenethacarb,fenfluthrin, fenfuram, fenhexamid, fenidin, fenitropan, fenitrothion,fénizon, fenjuntong, fenobucarb, fenolovo, fenoprop, fenothiocarb,fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-P, fenoxasulfone,fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin,fenpropimorph, fenpyrazamine, fenpyroximate, fenquinotrione, fenridazon,fenson, fensulfothion, fenteracol, fenthiaprop, fenthion,fenthion-ethyl, fentiaprop, fentin, fentrazamide, fentrifanil, fenuron,fenuron-TCA, fenvalerate, ferbam, ferimzone, ferric phosphate, ferroussulfate, fipronil, flamprop, flamprop-M, flazasulfuron, flocoumafen,flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop,fluazifop-P, fluazinarn, fluazolate, fluazuron, flubendiamide,flubenzimine, flubrocythrinate, flucarbazone, flucetosulfuron,fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil,fluenethyl, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican,flufenoxuron, flufenoxystrobin, flufenprox, flufenpyr, flufenzine,flufiprole, fluhexafon, flumethrin, flumetover, flumetralin,flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, flumorph,fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid,fluoroacetamide, fluoroacetic acid, fluorochloridone, fluorodifen,fluoroglycofen, fluoroimide, fluoromide, fluoromidine, fluoronitrofen,fluoroxypyr, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam,flupropacil, flupropadine, flupropanate, flupyradifurone,flupyrsulfuron, fluquinconazole, fluralaner, flurazole, flurecol,flurenol, fluridone, flurochloridone, fluromidine, fluroxypyr,flurprimidol, flursulamid, flurtarnone, flusilazole, flusulfamide,flutenzine, fluthiacet, fluthiamide, flutianil, flutolanil, flutriafol,fluvalinate, fluxapyroxad, fluxofenim, folpel, folpet, fomesafen,fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate,formothion, formparanate, fosamine, fosetyl, fosmethilan, fospirate,fosthiazate, fosthietan, frontalin, fthalide, fuberidazole, fucaojing,fucaomi, fujunmanzhi, fulumi, fumarin, funaihecaoling, fuphenthiourea,furalane, furalaxyl, furamethrin, furametpyr, furan tebufenozide,furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-BHC,garnma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellin A3,gibberellins, gliftor, glitor, glucochloralose, glufosinate,glufosinate-P, glyodin, glyoxirne, glyphosate, glyphosine, gossyplure,grandlure, griseofulvin, guanoctine, guazatine, halacrinate, halauxifen,halfenprox, halofenozide, halosafen, halosulfuron, haloxydine,haloxyfop, haloxyfop-P, haloxyfop-R, HCA, HCB, HCH, hemel, hempa, HEOD,heptachlor, heptafluthrin, heptenophos, heptopargil, herbimycin,herbimycin A, heterophos, hexachlor, hexachioran, hexachioroacetone,hexachlorobenzene, hexachiorobutadiene, hexachlorophene, hexaconazole,hexaflurnuron, hexafluoramin, hexaflurate, hexalure, hexamide,hexazinone, hexyithiofos, hexythiazox, HHDN, holosulf, homobrassinolide,huancaiwo, huanchongjing, huangcaoling, huanjunzuo, hydramethylnon,hydrargaphen, hydrated lime, hydrogen cyanamide, hydrogen cyanide,hydroprene, hydroxyisoxazole, hymexazol, hyquincarb, IAA, IBA, IBP,icaridin, imazalil, imazarnethabenz, imazamox, imazapic, imazapyr,imazaquin, imazethapyr, imazosulfuron, imibenconazole, imicyafos,imidacloprid, imidaclothiz, iminoctadine, imiprothrin, inabenfide,indanofan, indaziflam, indoxacarb, inezin, infusorial earth, iodobonil,iodocarb, iodofenphos, iodomethane, iodosulfuron, iofensulfuron,ioxynil, ipazine, IPC, ipconazole, ipfencarbazone, ipfentrifluconazole,iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol,IPSP, IPX, isamidofos, isazofos, isobenzan, isocarbamid, isocarbamide,isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl,isofetamid, isolan, isomethiozin, isonoruron, isopamphos, isopolinate,isoprocarb, isoprocil, isopropalin, isopropazol, isoprothiolane,isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron,isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxaflutole,isoxapyrifop, isoxathion, isuron, ivermectin, ixoxaben, izopamfos,izopamphos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonicacid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,jiecaoxi, Jinganmycin A, jodfenphos, juvenile hormone I, juvenilehormone II, juvenile hormone III, kadethrin, kappa-bifenthrin,kappa-tefluthrin, karbutilate, karetazan, kasugamycin, kejunlin,kelevan, ketospiradox, kieselguhr, kinetin, kinoprene, kiralaxyl,kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, leadarsenate, lenacil, lepimectin, leptophos, lianbenjingzhi, lime sulfur,lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron,lüxiancaolin, lvdingjunzhi, lvfumijvzhi, lvxiancaolin, lythidathion,M-74, M-81, MAA, magnesium phosphide, malathion, maldison, maleichydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb,mandestrobin, mandipropamid, maneb, matrine, mazidox, MCC, MCP, MCPA,MCPA-thioethyl, MCPB, MCPP, mebenil, mecarbam, mecarbinzid, mecarphon,mecoprop, mecoprop-P, medimeform, medinoterb, medlure, mefenacet,mefenoxam, mefenpyr, mefluidide, megatomoic acid, melissyl alcohol,melitoxin, MEMC, menazon, MEP, mepanipyrim, meperfluthrin, mephenate,mephosfolan, mepiquat, mepronil, meptyldinocap, mercaptodimethur,mercaptophos, mercaptophos thiol, mercaptothion, mercuric chloride,mercuric oxide, mercurous chloride, merphos, merphos oxide, mesoprazine,mesosulfuron, mesotrione, mesulfen, mesulfenfos, mesulphen, metacresol,metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metamifop,metamitron, metaphos, metaxon, metazachlor, metazosulfuron, metazoxolon,metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos,methalpropalin, metham, methamidophos, methasulfocarb, methazole,methfuroxam, methibenzuron, methidathion, methiobencarb, methiocarb,methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos,métholcarb, methometon, methomyl, methoprene, methoprotryn,methoprotryne, methoquin-butyl, methothrin, methoxychlor,methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyleugenol, methyl iodide, methyl isothiocyanate, methyl parathion,methylacetophos, methylchloroform, methyldithiocarbamic acid,methyldymron, methylene chloride, methyl-isofenphos, methylmercaptophos,methylmercaptophos oxide, methylmercaptophos thiol, methylmercurybenzoate, methylmercury dicyandiamide, methylmercurypentachlorophenoxide, methylneodecanamide, methylnitrophos,methyltriazothion, metiozolin, metiram, metiram-zinc, metobenzuron,metobrornuron, metofluthrin, metolachlor, metolcarb, metometuron,metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,metriam, metribuzin, metrifonate, metriphonate, metsulfovax,metsulfuron, mevinphos, mexacarbate, miechuwei, mieshuan, miewenjuzhi,milbemectin, milbemycin oxime, milneb, mima2nan, mipafox, MIPC, mirex,MNAF, moguchun, molinate, molosultap, momfluorothrin, monalide,monisuron, monoamitraz, monochloroacetic acid, monocrotophos,monolinuron, monomehypo, monosulfiram, monosulfuron, monosultap,monuron, monuron-TCA, morfamquat, moroxydine, morphothion, morzid,moxidectin, MPMC, MSMA, MTMC, muscalure, myclobutanil, myclozolin,myricyl alcohol, N-(ethylmercury)-p-toluenesulphonanilide, NAA, NAAm,nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalicanhydride, naphthalophos, naphthoxyacetic acids, naphthylacetic acids,naphthylindane-1,3-diones, naphthyloxyacetic acids, naproanilide,napropamide, napropamide-M, naptalam, natamycin, NBPOS, neburea,neburon, nendrin, neonicotine, nichlorfos, niclofen, niclosarnide,nicobifen, nicosulfuron, nicotine, nicotine sulfate, nifluridide,nikkomycins, NIP, nipyraclofen, nipyralofen, nitenpyram, nithiazine,nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen,nitrostyrene, nitrothal-isopropyl, nobormide, nonanol, norbormide,norea, norflurazon, nornicotine, noruron, novaluron, noviflumuron, NPA,nuarimol, nuranone, OCH, octachiorodipropyl ether, octhilinone,o-dichlorobenzene, ofurace, omethoate, o-phenylphenol, orbencarb,orfralure, orthobencarb, ortho-dichlorobenzene, orthosulfamuron,oryctalure, orysastrobin, oryzalin, osthol, osthole, ostramone, ovatron,ovex, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl,oxapyrazon, oxapyrazone, oxasulfuron, oxathiapiprolin, oxaziclomefone,oxine-copper, oxine-Cu, oxolinic acid, oxpoconazole, oxycarboxin,oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyenadenine,oxyfluorfen, oxymatrine, oxytetracycline, oxythioquinox, PAC,paclobutrazol, paichongding, palléthrine, PAP, para-dichlorobenzene,parafluron, paraquat, parathion, parathion-methyl, parinol, Paris green,PCNB, PCP, PCP-Na, p-dichlorobenzene, PDJ, pebulate, pédinex,pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin,penfenate, penflufen, penflufen, penoxalin, penoxsulam,pentachlorophenol, pentachlorophenyl laurate, pentanochlor,penthiopyrad, pentmethrin, pentoxazone, perchlordecone, perfluidone,permethrin, pethoxamid, PHC, phenamacril, phenamacril-ethyl,phenaminosulf, phenazine oxide, phénétacarbe, phenisopham, phenkapton,phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothiol, phenothrin,phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate,phenylmercury chloride, phenylmercury derivative of pyrocatechol,phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim,phosalone, phosametine, phosazetim, phosazetin, phoscyclotin,phosdiphen, phosethyl, phosfolan, phosfolan-methyl, phosglycin, phosmet,phosnichior, phosphamide, phosphamidon, phosphine, phosphinothricin,phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide,phthalophos, phthalthrin, picarbutrazox, picaridin, picloram,picolinafen, picoxystrobin, pimaricin, pindone, pinoxaden, piperalin,piperazine, piperonyl butoxide, piperonyl cyclonene, piperophos,piproctanly, piproctanyl, piprotal, pirimetaphos, pirimicarb, piriminil,pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, pival, pivaldione,plifenate, PMA, PMP, polybutenes, polycarbamate, polychlorcamphene,polyethoxyquinoline, polyoxin D, polyoxins, polyoxorim, polythialan,potassium arsenite, potassium azide, potassium cyanate, potassiumethylxanthate, potassium naphthenate, potassium polysulfide, potassiumthiocyanate, pp′-DDT, prallethrin, precocene I, precocene II, precoceneIII, pretilachlor, primidophos, primisulfuron, probenazole, prochloraz,proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,profluralin, profluthrin, profoxydim, profurite-aminium, proglinazine,prohexadione, prohydrojasmon, promacyl, promecarb, prometon, prometryn,prometryne, promurit, pronamide, propachior, propafos, propamidine,propamocarb, propanil, propaphos, propaquizafop, propargite,proparthrin, propazine, propetamphos, propharn, propiconazole,propidine, propineb, propisochior, propoxur, propoxycarbazone, propylisome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin,prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothioconazole,prothiofos, prothoate, protrifenbute, proxan, prymidophos, prynachlor,psoralen, psoralene, pydanon, pyflubumide, pymetrozine, pyracarbolid,pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyrafluprole,pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyraziflumid,pyrazolate, pyrazolynate, pyrazon, pyrazophos, pyrazosulfuron,pyrazothion, pyrazoxyfen, pyresrnethrin, pyrethrin I, pyrethrin II,pyrethrins, pyribarnbenz-isopropyl, pyribambenz-propyl, pyribencarb,pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,pyridaphenthion, pyridaphenthione, pyridate, pyridinitril, pyrifenox,pyrifluquinazon, pyriftalid, pyrimétaphos, pyrimethanil, pyrimicarbe,pyrimidifen, pyriminobac, pyriminostrobin, pyrimiphos-éthyl,pyrimiphos-méthyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone,pyriprole, pyripropanol, pyriproxyfen, pyrisoxazole, pyrithiobac,pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychior, pyroxyfur,qincaosuan, qingkuling, quassia, quinacetol, quinalphos,quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac,quinoclamine, quinomethionate, quinonamid, quinothion, quinoxyfen,quintiofos, quintozene, quizalofop, quizalofop-P, quwenzhi, quyingding,rabenzazole, rafoxanide, R-diniconazole, rebemide, regione, renriduron,rescalure, resrnethrin, rhodethanil, rhodojaponin-III, ribavirin,rimsulfuron, rizazole, R-metalaxyl, rodéthanil, runnel, rotenone,ryania, sabadilla, saflufenacil, saijunmao, saisentong, salicylanilide,salifluofen, sanguinarine, santonin, S-bioallethrin, schradan,scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin,semiamitraz, sesamex, sesamolin, sesone, sethoxydim, sevin,shuangjiaancaolin, shuangjianancaolin, S-hydroprene, siduron,sifumijvzhi, siglure, silafluofen, silatrane, silica aerogel, silicagel, silthiofam, silthiopham, silthiophan, silvex, simazine,simeconazole, simeton, simetryn, simetryne, sintofen, S-kinoprene,slaked lime, SMA, S-methoprene, S-metolachlor, sodium arsenite, sodiumazide, sodium chlorate, sodium cyanide, sodium fluoride, sodiumfluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodiumo-phenylphenoxide, sodium orthophenyiphenoxide, sodiumpentachiorophenate, sodium pentachlorophenoxide, sodium polysulfide,sodium silicofluoride, sodium tetrathiocarbonate, sodium thiocyanate,solan, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen,spirotetramat, spiroxamine, stirofos, streptomycin, strychnine,sulcatol, sulcofuron, sulcotrione, sulfallate, sulfentrazone, sulfiram,suifluramid, sulfodiazole, sulfometuron, sulfosate, sulfosulfuron,sulfotep, sulfotepp, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuricacid, sulfuryl fluoride, sulglycapin, sulphosate, sulprofos, sultropen,swep, tau-fluvalinate, tavron, tazimcarb, TBTO, TBZ, TCA, TCBA, TCMTB,TCNB, IDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin,tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram,tedion, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temefos,temephos, tepa, TEPP, tepraloxydim, tepraloxydim, terallethrin,terbacil, terbucarb, terbuchior, terbufos, terbumeton, terbuthylazine,terbutol, terbutryn, terbutryne, terraclor, terramicin, terramycin,tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole,tetradifon, tetradisul, tetrafluron, tetramethrin, tetramethylfluthrin,tetramine, tetranactin, tetraniliprole, tetrapion, tetrasul, thalliumsulfate, thallous sulfate, thenylchlor, theta-cypermethrin,thiabendazole, thiacloprid, thiadiazine, thiadifluor, thiamethoxam,thiameturon, thiapronil, thiazafluron, thiazfluron, thiazone, thiazopyr,thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone,thifensulfuron, thifluzamide, thimerosal, thimet, thiobencarb,thiocarboxime, thiochlorfenphim, thiochlorphenphime,thiocyanatodinitrobenzenes, thiocyclam, thiodan, thiodiazole-copper,thiodicarb, thiofanocarb, thiofanox, thiofluoximate, thiohempa,thiomersal, thiometon, thionazin, thiophanate, thiophanate-ethyl,thiophanate-methyl, thiophos, thioquinox, thiosemicarbazide, thiosultap,thiotepa, thioxamyl, thiram, thiuram, thuringiensin, tiabendazole,tiadinil, tiafenacil, tiaojiean, TIBA, tifatol, tiocarbazil, tioclorim,tioxazafen, tioxymid, tirpate, TMTD, tolclofos-methyl, tolfenpyrad,tolprocarb, tolpyralate, tolyfluanid, tolylfluanid, tolylmercuryacetate, tomarin, topramezone, toxaphene, TPN, tralkoxydim,tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin,tretamine, triacontanol, triadirnefon, triadirnenol, triafamone,triallate, tri-allate, triamiphos, triapenthenol, triarathene,triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos,triazothion, triazoxide, tribasic copper chloride, tribasic coppersulfate, tribenuron, tribufos, tributyltin oxide, tricamba, trichlamide,trichlopyr, trichlorfon, trichlormetaphos-3, trichloronat,trichloronate, trichlorotrinitrobenzenes, trichlorphon, triclopyr,triclopyricarb, tricresol, tricyclazole, tricyclohexyltin hydroxide,tridemorph, tridiphane, trietazine, trifenmorph, trifenofos,trifloxystrobin, trifloxysulfuron, trifludimoxazin, triflumezopyrim,triflumizole, triflumuron, trifluralin, triflusulfuron, trifop,trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb,trimeturon, trinexapac, triphenyltin, triprene, tripropindan,triptolide, tritac, trithialan, triticonazole, tritosulfuron,trunc-call, tuoyelin, uniconazole, uniconazole-P, urbacide, uredepa,valerate, validamycin, validamycin A, valifenalate, valone, vamidothion,vangard, vaniliprole, vernolate, vinclozolin, vitamin D3, warfarin,xiaochongliulin, xinjunan, xiwojunan, xiwojunzhi, XMC, xylachlor,xylenols, xylylcarb, xymiazole, yishijing, zarilamid, zeatin,zengxiaoan, zengxiaolin, zeta-cypermethrin, zinc naphthenate, zincphosphide, zinc thiazole, zinc thiozole, zinc trichlorophenate, zinctrichlorophenoxide, zineb, ziram, zolaprofos, zoocoumarin, zoxamide,zuoanjunzhi, zuocaoan, zuojunzhi, zuomihuanglong, α-chlorohydrin,α-ecdysone, α-multistriatin, α-naphthaleneacetic acids, and β-ecdysone;

(2) the following molecule

N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide

In this document, this molecule, for ease of use, is named as “AI-1;”

(3) a molecule known as Lotilaner which has the following structure

and

(4) the following molecules in Table A

TABLE A Structure of M - active ingredients Name Structure M1

M2

M3

M4

M5

M6

As used in this disclosure, each of the above is an active ingredient,and two or more are active ingredients. For more information consult the“COMPENDIUM OF PESTICIDE COMMON NAMES” located at Alanwood.net andvarious editions, including the on-line edition, of “THE PESTICIDEMANUAL” located at bcpcdata.com.

The term “alkenyl” means an acyclic, unsaturated (at least onecarbon-carbon double bond), branched or unbranched, substituentconsisting of carbon and hydrogen, for example, vinyl, allyl, butenyl,pentenyl, and hexenyl.

The term “alkenyloxy” means an alkenyl further consisting of acarbon-oxygen single bond, for example, allyloxy, butenyloxy,pentenyloxy, hexenyloxy.

The term “alkoxy” means an alkyl further consisting of a carbon-oxygensingle bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, and tert-butoxy.

The term “alkyl” means an acyclic, saturated, branched or unbranched,substituent consisting of carbon and hydrogen, for example, methyl,ethyl, propyl, isopropyl, butyl, and tert-butyl.

The term “alkynyl” means an acyclic, unsaturated (at least onecarbon-carbon triple bond), branched or unbranched, substituentconsisting of carbon and hydrogen, for example, ethynyl, propargyl,butynyl, and pentynyl.

The term “alkynyloxy” means an alkynyl further consisting of acarbon-oxygen single bond, for example, pentynyloxy, hexynyloxy,heptynyloxy, and octynyloxy.

The term “aryl” means a cyclic, aromatic substituent consisting ofhydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.

The term “biopesticide” means a microbial biological pest control agentwhich, in general, is applied in a similar manner to chemicalpesticides. Commonly they are bacterial, but there are also examples offungal control agents, including Trichoderma spp. and Ampelomycesquisqualis. One well-known biopesticide example is Bacillusthuringiensis, a bacterial disease of Lepidoptera, Coleoptera, andDiptera. Biopesticides include products based on:

(1) entomopathogenic fungi (e.g. Metarhizium anisopliae);

(2) entomopathogenic nematodes (e.g. Steinernema feltiae); and

(3) entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are notlimited to, baculoviruses, protozoa, and Microsporidia. For theavoidance of doubt biopesticides are considered to be activeingredients.

The term “cycloalkenyl” means a monocyclic or polycyclic, unsaturated(at least one carbon-carbon double bond) substituent consisting ofcarbon and hydrogen, for example, cyclobutenyl, cyclopentenyl,cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl,hexahydronaphthyl, and octahydronaphthyl.

The term “cycloalkenyloxy” means a cycloalkenyl further consisting of acarbon-oxygen single bond, for example, cyclobutenyloxy,cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

The term “cycloalkyl” means a monocyclic or polycyclic, saturatedsubstituent consisting of carbon and hydrogen, for example, cyclopropyl,cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, anddecahydronaphthyl.

The term “cycloalkoxy” means a cycloalkyl further consisting of acarbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy,cyclopentyloxy, norbornyloxy, and bicyclo[2.2.2]octyloxy.

The term “halo” means fluoro, chloro, bromo, and iodo.

The term “haloalkoxy” means an alkoxy further consisting of, from one tothe maximum possible number of identical or different, halos, forexample, fluoromethoxy, trifluorornethoxy, 2,2-difluoropropoxy,chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, andpentafluoroethoxy.

The term “haloalkyl” means an alkyl further consisting of, from one tothe maximum possible number of, identical or different, halos, forexample, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl,chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

The term “heterocyclyl” means a cyclic substituent that may be aromatic,fully saturated, or partially or fully unsaturated, where the cyclicstructure contains at least one carbon and at least one heteroatom,where said heteroatom is nitrogen, sulfur, or oxygen. Examples are:

(1) aromatic heterocyclyl substituents include, but are not limited to,benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl,benzothienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl,imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl,quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl,triazinyl, and triazolyl;

(2) fully saturated heterocyclyl substituents include, but are notlimited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl,tetrahydrofuranyl, and tetrahydropyranyl;

(3) partially or fully unsaturated heterocyclyl substituents include,but are not limited to, 1,2,3,4-tetrahydro-quinolinyl,4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl,and 2,3-dihydro-[1,3,4]-oxadiazolyl; and

(4) Additional examples of heterocyclyls include the following:

The term “locus” means a habitat, breeding ground, plant, seed, soil,material, or environment, in which a pest is growing, may grow, or maytraverse, for example, a locus may be: where crops, trees, fruits,cereals, fodder species, vines, turf, and/or ornamental plants aregrowing; where domesticated animals are residing; the interior orexterior surfaces of buildings (such as places where grains are stored);the materials of construction used in buildings (such as impregnatedwood); and the soil around buildings.

The phrase “MoA Material” means a material having a mode of action(“MoA”) as indicated in IRAC MoA Classification v. 7.3, located atirac-online.org., which describes:

(1) Acetylcholinesterase (ACNE) inhibitors;

(2) GABA-gated chloride channel antagonists;

(3) Sodium channel modulators;

(4) Nicotinic acetylcholine receptor (nAChR) agonists;

(5) Nicotinic acetylcholine receptor (nAChR) allosteric activators;

(6) Chloride channel activators;

(7) Juvenile hormone mimics;

(8) Miscellaneous nonspecific (multi-site) inhibitors;

(9) Modulators of Chordotonal Organs;

(10) Mite growth inhibitors;

(11) Microbial disruptors of insect midgut membranes;

(12) Inhibitors of mitochondrial ATP synthase;

(13) Uncouplers of oxidative phosphorylation via disruption of theproton gradient;

(14) Nicotinic acetylcholine receptor (nAChR) channel blockers;

(15) Inhibitors of chitin biosynthesis, type 0;

(16) Inhibitors of chitin biosynthesis, type 1;

(17) Moulting disruptor, Dipteran;

(18) Ecdysone receptor agonists;

(19) Octopamine receptor agonists;

(20) Mitochondrial complex III electron transport inhibitors;

(21) Mitochondrial complex I electron transport inhibitors;

(22) Voltage-dependent sodium channel blockers;

(23) Inhibitors of acetyl CoA carboxylase;

(24) Mitochondrial complex IV electron transport inhibitors;

(25) Mitochondrial complex II electron transport inhibitors; and

(28) Ryanodine receptor modulators.

The phrase “MoA material group alpha” (hereafter “MoAMGA”) meanscollectively the following materials, abamectin, acephate, acequinocyl,acetamiprid, acrinathrin, alanycarb, aldicarb, allethrin,alpha-cypermethrin, aluminium phosphide, amitraz, azamethiphos,azinphos-ethyl, azinphos-methyl, azocyclotin, bendiocarb, benfuracarb,bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin,bioallethrin S-cyclopentenyl isomer, bioresmethrin, bistrifluron, borax,buprofezin, butocarboxim, butoxycarboxim, cadusafos, calcium phosphide,carbaryl, carbofuran, carbosulfan, cartap hydrochloride,chlorantraniliprole, chlordane, chlorethoxyfos, chlorfenapyr,chlorfenvinphos, chlorfluazuron, chiormephos, chloropicrin,chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezine,clothianidin, coumaphos, cyanide, cyanophos, cyantraniliprole,cycloprothrin, cyenopyrafen, cyflumetofen, cyfluthrin, cyhalothrin,cyhexatin, cypermethrin, cyphenothrin cyromazine, d-cis-trans-allethrin,DDT, deltamethrin, demeton-S-methyl, diafenthiuron, diazinon,dichlorvos/DDVP, dicrotophos, diflovidazin, diflubenzuron, dimethoate,dimethylvinphos, dinotefuran, disulfoton, DNOC, d-trans-allethrin,emamectin benzoate, empenthrin endosulfan, EPN, esfenvalerate,ethiofencarb, ethion, ethoprophos, etofenprox, etoxazole, famphur,fenamiphos, fenazaquin, fenbutatin oxide, fenitrothion, fenobucarb,fenoxycarb, fenpropathrin, fenpyroximate, fenthion, fenvalerate,flonicamid, fluacrypyrim, flubendiamide, flucycloxuron, flucythrinate,flufenoxuron, flumethrin, flupyradifurone, formetanate, fosthiazate,furathiocarb, gamma-cyhalothrin, halfenprox, halofenozide, heptenophos,hexaflumuron, hexythiazox, hydramethylnon, hydroprene, imicyafos,imidacloprid, imiprothrin, indoxacarb, isofenphos, isoprocarb,isoxathion, kadethrin, kinoprene, lambda-cyhalothrin, lepimectin,lufenuron, malathion, mecarbam, metaflumizone, methamidophos,methidathion, methiocarb, methomyl, methoprene,(methoxyaminothio-phosphoryl) salicylate, methoxychlor, methoxyfenozide,methyl bromide, metolcarb, mevinphos, milbemectin, monocrotophos, naled,nicotine, nitenpyram, novaluron, noviflumuron, oxamyl,oxydemeton-methyl, parathion, parathion-methyl, permethrin, phenothrin,phenthoate, phorate, phosalone, phosmet, phosphamidon, phosphine,phoxim, pirimicarb, pirimiphos-methyl, prallethrin, profenofos,propargite, propetamphos, propoxur, prothiofos, pymetrozine, pyraclofos,pyrethrin, pyridaben, pyridaphenthion, pyrimidifen, pyriproxyfen,quinalphos, resmethrin, rotenone, silafluofen, spinetoram, spinosad,spirodiclofen, spiromesifen, spirotetramat, sulfluramid, sulfotep,sulfoxaflor, sulfuryl fluoride, tartar emetic, tau-fluvalinate,tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin,temephos, terbufos, tetrachlorvinphos, tetradifon, tetramethrin,tetramethrin, theta-cypermethrin, thiacloprid, thiarnethoxam,thiocyclam, thiodicarb, thiofanox, thiometon, thiosultap-sodium,tolfenpyrad, tralomethrin, transfluthrin, triazarnate, triazophos,trichlorfon, triflumuron, trimethacarb, vamidothion, XMC, xylylcarb,zeta-cypermethrin, and zinc phosphide. For the avoidance of doubt, eachof the foregoing materials is an active ingredient.

The term “pest” means an organism that is detrimental to humans, orhuman concerns (such as, crops, food, livestock, etc.), where saidorganism is from Phyla Arthropoda, Mollusca, or Nematoda, particularexamples are ants, aphids, beetles, bristletails, cockroaches, crickets,earwigs, fleas, flies, grasshoppers, leafhoppers, lice (including sealice), locusts, mites, moths, nematodes, scales, symphylans, termites,thrips, ticks, wasps, and whiteflies, additional examples are pests in:

(1) Subphyla Chelicerata, Myriapoda, Crustacea, and Hexapoda;

(2) Classes of Arachnida, Maxillopoda, Symphyla, and Insecta;

(3) Order Anoplura. A non-exhaustive list of particular genera includes,but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathusspp., Pediculus spp., and Polyplax spp. A non-exhaustive list ofparticular species includes, but is not limited to, Haematopinus asini,Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculushumanus capitis, Pediculus humanus humanus, and Pthirus pubis.

(4) Order Coleoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Acanthoscelides spp., Agriotes spp.,Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchusspp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnemaspp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp.,Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp.,Meligethes spp., Otiorhynchus spp., Pantornorus spp., Phyllophaga spp.,Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp.,Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. Anon-exhaustive list of particular species includes, but is not limitedto, Acanthoscelides obtectus, Agrilus planipennis, Anoplophoraglabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis,Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus,Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcate,Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris,Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Criocerisasparagi, Cryptolestes ferruginous, Cryptolestes pusMus, Cryptolestesturcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermesteslardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae,Hylobius pales, Hypera postica, Hypothenemus hampei, Lasiodermaserricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenyssuturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotuscommunis, Meligethes aeneus, Melolontha melolontha, Oberea brevis,Qberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilussurinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana,Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica, Sitonalineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais,Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogodermavariabile, and Zabrus tenebrioides.

(5) Order Dermaptera. A non-exhaustive list of particular speciesincludes, but is not limited to, Forficula auricularia.

(6) Order Blattaria. A non-exhaustive list of particular speciesincludes, but is not limited to, Blattella germanica, Blatta orientalis,Parcoblatta pennsylvanica, Periplaneta americana, Periplanetaaustralasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelussurinamensis, and Supella longipalpa.

(7) Order Diptera. A non-exhaustive list of particular genera includes,but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp.,Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp.,Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Deliaspp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Muscaspp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive listof particular species includes, but is not limited to, Agromyzafrontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa,Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens,Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Deliaplatura, Fannia canicularis, Fannia scalaris, Gasterophilusintestinalis, Gracillia perseae, Haematobia irritans, Hypodermalineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis,Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psilarosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax,Sitodiplosis inosellana, and Stomoxys calcitrans.

(8) Order Hemiptera. A non-exhaustive list of particular generaincludes, but is not limited to, Adelges spp., Aulacaspis spp.,Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspisspp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp.,Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezaraspp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcusspp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphisspp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp.and Unaspis spp. A non-exhaustive list of particular species includes,but is not limited to, Acrosternum hi/are, Acyrthosiphon pisum,Aleyrodes proletella, Aleurodicus disperses, Aleurothrixus floccosus,Amrasca biguttula biguttula, Aonidiella aurantil, Aphis gossypil, Aphisglycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisiatabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi,Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimexhemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus,Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercussuturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura,Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltistheivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus,Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus,Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphumgranariurn, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarvafrimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae,Nephotettix cinctipes, Neumcolpus longirostris, Nezara viridula,Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinusmaidis, Phylloxera vitifoliae, Physokermes piceae, Phytocoriscalifornicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsuslineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcusbrevipes, Quadraspidiotus perniciosus, Rhopalosiphurn maidis,Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphisgraminurn, Sitobion a venae, Sogatella furcifera, Trialeurodesvaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zuliaentrerriana.

(9) Order Hymenoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Acrornyrmex spp., Atta spp., Camponotusspp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp.,Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., andXylocopa spp. A non-exhaustive list of particular species includes, butis not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis,Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsisgeminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni,and Tapinoma sessile.

(10) Order Isoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Coptotermes spp., Cornitermes spp.,Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermesspp., Macrotermes spp., Marginitermes spp., Microcerotermes spp.,Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., andZootermopsis spp. A non-exhaustive list of particular species includes,but is not limited to, Coptotermes curvignathus, Coptotermes frenchi,Coptotermes formosanus, Heterotermes aureus, Microtermes obese,Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermesflavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermessantonensis, Reticulitermes speratus, Reticulitermes tibialis, andReticulitermes virginicus.

(11) Order Lepidoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Adoxophyes spp., Agrotis spp.,Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp.,Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraeaspp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortynaspp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletisspp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycterspp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp.,and Yponomeuta spp. A non-exhaustive list of particular speciesincludes, but is not limited to, Achaea Janata, Adoxophyes orana,Agrotis Ipsilon, Alabama argillacea, Amorbia cuneana, Amyeloistransitella, Anacamptodes defectaria, Anarsia lineatella, Anomissabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana,Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbocinnara, Bucculatrix thurberiella, Capua reticulana, Carposinaniponensis, Chlumetia transversa, Choristoneura rosaceana,Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydiacaryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydiapomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella,Earias insulana, Earias vittella, Ecdytolopha aurantianurn, Elasmopalpuslignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella,Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoeciliaambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata,Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellulaundalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucopteracoffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotisalbicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti,Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta,Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata,Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemisheparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia,Peri/eucoptera coffeella, Phthorimaea operculella, Phyllocnistiscitre/la, Pieris rapae, Plathypena scabra, Plodia interpunctella,Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae,Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu,Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setoranitens, Sitotroga cerealella, Sparganothis pilleriana, Spodopteraexigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides,Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae,and Zeuzera pyrina;

(12) Order Mallophaga. A non-exhaustive list of particular generaincludes, but is not limited to, Anaticola spp., Bovicola spp.,Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp.A non-exhaustive list of particular species includes, but is not limitedto, Bovicola bovis, Bovicola caprae, Bovicola avis, Chelopistesmeleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthusstramineus, Menopon gallinae, and Trichodectes canis.

(13) Order Orthoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Melanoplus spp., and Pterophylla spp. Anon-exhaustive list of particular species includes, but is not limitedto, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis,Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria,Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.

(14) Order Siphonaptera. A non-exhaustive list of particular speciesincludes, but is not limited to, Ceratophyllus gallinae, Ceratophyllusniger, Ctenocephalides canis, Ctenocephalides fells, and Pulex irritans.

(15) Order Siphonostomatoida. A non-exhaustive list of particularspecies includes, but is not limited to, Lepeophtheirus salmonis,Lepeophtheirus pectoralis, Caligus elongatus, and Caligus ciemensi.

(16) Order Thysanoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Caliothrips spp., Frankliniella spp.,Scirtothrips spp., and Thrips spp. A non-exhaustive list of particularspecies includes, but is not limited to, Frankliniella fusca,Frankliniella occidentalis, Frankliniella schultzei, Frankliniellawilliamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus,Scirtothrips citri, Scirtothrips dorsalis, Taeniothripsrhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thripsorientalis, and Thrips tabaci.

(17) Order Thysanura. A non-exhaustive list of particular generaincludes, but is not limited to, Lepisma spp. and Thermobia spp.

(18) Order Acarina. A non-exhaustive list of particular genera includes,but is not limited to, Acarus spp., Aculops spp., Boophilus spp.,Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodesspp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., andTetranychus spp. A non-exhaustive list of particular species includes,but is not limited to, Acarapis woodi, Acarus sire, Aceria mangiferae,Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyommaamericanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentorvariabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini,Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychuscitri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemuslatus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophusperseaflorae, Tetranychus urticae, and Varroa destructor.

(19) Order Symphyla. A non-exhaustive list of particular speciesincludes, but is not limited to, Scutigerella immaculata.

(20) Phylum Nematoda. A non-exhaustive list of particular generaincludes, but is not limited to, Aphelenchoides spp., Belonolaimus spp.,Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniellaspp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., andRadopholus spp. A non-exhaustive list of particular sp. includes, but isnot limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyneincognita, Meloidogyne javanica, Onchocerca volvulus, Radopholussimilis, and Rotylenchulus reniformis.

The phrase “pesticidally effective amount” means the amount of apesticide needed to achieve an observable effect on a pest, for example,the effects of necrosis, death, retardation, prevention, removal,destruction, or otherwise diminishing the occurrence and/or activity ofa pest in a locus, this effect may come about when, pest populations arerepulsed from a locus, pests are incapacitated in, or around, a locus,and/or pests are exterminated in, or around, a locus. Of course, acombination of these effects can occur. Generally, pest populations,activity, or both are desirably reduced more than fifty percent,preferably more than 90 percent, and most preferably more than 99percent. In general a pesticidally effective amount, for agriculturalpurposes, is from about 0.0001 grams per hectare to about 5000 grams perhectare, preferably from about 0.0001 grams per hectare to about 500grams per hectare, and it is even more preferably from about 0.0001grams per hectare to about 50 grams per hectare.

DETAILED DESCRIPTION OF THE DISCLOSURE

This document discloses molecules of Formula One

wherein:

(A) R¹, R⁵, R⁶, R¹¹, R¹², R¹³, and R¹⁴ are each independently selectedfrom the group consisting of H, F, Cl, Br, I, CN, (C₁-C₄)alkyl,(C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy;

(B) R², R³, and R⁴ are each independently selected from the groupconsisting of H, F, Cl, Br, I, CN, (C₁-C₄)alkyl, (C₂-C₄)alkenyl,(C₂-C₄)alkynyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy;

(C) R⁷ is (C₁-C₆)haloalkyl;

(D) R⁹ is selected from the group consisting of (F), H, F, Cl, Br, I,CN, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and(C₁-C₄)haloalkoxy;

(E) R¹⁰ is selected from the group consisting of (F), F, Cl, Br, I, CN,(C₁-C₄)alkyl, (C₂-C₄)alkenyl, (C₂-C₄)alkynyl, (C₁-C₄)haloalkyl,(C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy;

(F) R⁹ and R¹⁰ together can optionally form a 3- to 5-membered saturatedor unsaturated, hydrocarbyl link,

wherein said hydrocarbyl link may optionally be substituted with one ormore substituents independently selected from the group consisting of F,Cl, Br, I, and CN;

(G) L is (C₁-C₆)alkyl;

(H) X is selected from the group consisting of C, S, and P(C₁-C₆)alkyl;

(I) n is 1 or 2;

(J) R¹⁵ is selected from the group consisting of (C₁-C₄)alkyl,(C₂-C₄)alkenyl, (C₃-C₄)cycloalkyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy,(C₁-C₄)haloalkoxy, phenyl, and NH(C₃-C₄)cycloalkyl,

-   -   wherein each alkyl, alkenyl, cycloalkyl, haloalkyl, alkoxy,        haloalkoxy, and phenyl may optionally be substituted with one or        more substituents independently selected from the group        consisting of F, Cl, Br, I, CN, and OH; and

agriculturally acceptable acid addition salts, salt derivatives,solvates, ester derivatives, crystal polymorphs, isotopes, resolvedstereoisomers, and tautomers, of the molecules of Formula One.

In another embodiment R¹, R³, R⁴, R⁵, R⁶, R⁹, R¹¹, R¹², R¹³, and R¹⁴ areH. This embodiment may be used in combination with the other embodimentsof R², R⁷, R¹⁰, L, X, n, and R¹⁵.

In another embodiment R² is Cl, Br, or CH₃. This embodiment may be usedin combination with the other embodiments of R¹, R³, R⁴, R⁵, R⁶, R⁷, R⁹,R¹⁰, R¹¹, R¹², R¹³, L, R¹⁴, X, n, and R¹⁵.

In another embodiment R³ is F, Cl, Br, or CH═CH₂. This embodiment may beused in combination with the other embodiments of R¹, R², R⁴, R⁵, R⁶,R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, L, R¹⁴, X, n, and R¹⁵.

In another embodiment R⁴ is Cl, Br, or CH₃. This embodiment may be usedin combination with the other embodiments of R¹, R², R³, R⁵, R⁶, R⁷, R⁹,R¹⁰, R¹¹, R¹², R¹³, L, R¹⁴, X, n, and R¹⁵.

In another embodiment R², R³, and R⁴ are CL This embodiment may be usedin combination with the other embodiments of R¹, R⁵, R⁶, R⁷, R⁹, R¹⁰,R¹¹, R¹², R¹³, L, R¹⁴, X, n, and R¹⁵.

In another embodiment R⁷ is (C₁-C₆)haloalkyl. This embodiment may beused in combination with the other embodiments of R¹, R², R³, R⁴, R⁵,R⁶, R⁹, R¹⁰, R¹¹, R¹², R¹³, L, R¹⁴, X, n, and R¹⁵.

In another embodiment R⁷ is CF₃, CF₂CH₃, or CF₂CH₂CH₃ This embodimentmay be used in combination with the other embodiments of R¹, R², R³, R⁴,R⁵, R⁶, R⁹, R¹⁰, R¹¹, R¹², R¹³, L, R¹⁴, X, n, and R¹⁵.

In another embodiment R¹⁰ is Cl, Br, I, CH₃, or CF₃. This embodiment maybe used in combination with the other embodiments of R¹, R², R³, R⁴, R⁵,R⁶, R⁷, R⁹, R¹¹, R¹², R¹³, L, R¹⁴, X, n, and R¹⁵.

In another embodiment L is CH(CH₃) or CH(CH₂CH₃). This embodiment may beused in combination with the other embodiments of R¹, R², R³, R⁴, R⁵,R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, X, n, and R¹⁵.

In another embodiment X is C or S. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁹, R¹⁰, R¹¹, R¹², R¹³, L, R¹⁴, n, and R¹⁵.

In another embodiment n is 1 or 2. This embodiment may be used incombination with the other embodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁹, R¹⁰, R¹¹, R¹², R¹³, L, R¹⁴, X, and R¹⁵.

In another embodiment R¹⁵ is CH₂CH₃, cyclopropyl, CH₂CF₃, CH₂CH₂CF₃, orNHcyclopropyl. This embodiment may be used in combination with the otherembodiments of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴,X, and n.

In another embodiment:

(A) R¹, R⁵, R⁶, R¹¹, R¹², R¹³, and R¹⁴ are H;

(B) R², R³, and R⁴ are each independently selected from the groupconsisting of H, F, Cl, Br, (C₁-C₄)alkyl, (C₂-C₄)alkenyl;

(C) R⁷ is (C₁-C₆)haloalkyl;

(D) R⁹ is H;

(E) R¹⁰ is selected from the group consisting of Cl, Br, (C₁-C₄)alkyl,and (C₁-C₄)haloalkyl;

(G) L is (C₁-C₆)alkyl;

(H) X is C or S;

(I) n is 1 or 2;

(J) R¹⁵ is selected from the group consisting of (C₁-C₄)alkyl,(C₃-C₄)cycloalkyl, (C₁-C₄)haloalkyl, and NH(C₃-C₄)cycloalkyl, whereineach alkyl, alkenyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, andphenyl may optionally be substituted with one or more substituentsindependently selected from the group consisting of F, Cl, Br, I, CN,and OH.

Preparation of Benzyl Halides

Benzyl alcohol 1-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are aspreviously disclosed, may be prepared in several ways. Ketones 1-1 maybe prepared by treating bromobenzenes with a lithium base such asn-butyllithium in a polar, aprotic solvent preferably diethyl ether attemperatures from about −78° C. to about 0° C. followed by treatmentwith esters R⁷C(O)O(C₁-C₄)alkyl, wherein R⁷ is as previously disclosed,such as ethyl 2,2-difluoropropanoate (not shown). Treatment of ketones1-1, wherein R¹, R², R³, R⁴, R⁵, and R⁷ are as previously disclosed,with a reducing agent such as sodium borohydride, in the presence of abase, such as aqueous sodium hydroxide, in a polar, protic solventpreferably methanol at about −10° C. to about 10° C. may provide benzylalcohols 1-3 (Scheme 1, step a). Alternatively, aldehydes 1-2, whereinR⁶ is H and R¹, R², R³, R⁴, and R⁵ are as previously disclosed, may beallowed to react with trifluorotrimethylsilane in the presence of acatalytic amount of tetrabutylammonium fluoride in a polar, aproticsolvent preferably tetrahydrofuran (Scheme 1, step b) to provide benzylalcohols 1-3, wherein R⁷ is CF₃. Subsequently, benzyl alcohols 1-3 maybe converted into benzyl halides 1-4, wherein E is Br, CI, or I, and R¹,R², R³, R⁴, R⁵, R⁶, and R⁷ are as previously disclosed, by treatmentwith a halogenating reagent, such as N-bromosuccinimide, andtriethylphosphite in a solvent that does not react with thereagents—preferably dichloromethane—at about 40° C. to provide benzylhalides 1-4, E is Br (Scheme 1, step c). Alternatively, benzyl alcohols1-3 may be converted into benzyl halides 1-4, where E is Br by treatmentwith a sulfonyl chloride such as methanesulfonyl chloride in thepresence of a base such as triethylamine and subsequent treatment of theresultant sulfonate with a transition metal bromide such as iron(III)bromide. Additionally, treatment with chlorinating reagents such asthionyl chloride in the presence of a base such as pyridine in ahydrocarbon solvent such as toluene at about 110° C. may provide benzylhalides 1-4, where E is Cl (Scheme 1, step c).

Preparation of Fluorinated Vinylbenzoic Esters and Acids

Halobenzoic acids 2-1, wherein R⁹, R¹⁰, R¹¹, and R¹² are as previouslydisclosed may be converted to halobenzoic acid esters 2-2, wherein R⁹,R¹⁰, R¹¹, and R¹² are as previously disclosed. Halobenzoic acids 2-1,may be treated with an acid, such as sulfuric acid, in the presence of a(C₁-C₈)alcohol such as ethanol, to provide halobenzoic acid ethyl esters2-2 (Scheme 2, step a). Fluorinated vinylbenzoic acid esters 2-3 may beaccessed via reaction of 2-2 with a fluorinated vinyl silane in thepresence of a palladium catalyst such astetrakis(triphenylphospine)palladium(0), a copper additive such ascopper(I) iodide, and a fluoride source, such as cesium fluoride in apolar, aprotic solvent preferably 1,3-dimethyl-2-imidazolidinone attemperatures ranging from about ambient temperature to about 45° C., toprovide fluorinated vinyl benzoic acid esters 2-3 (Scheme 2, step b).Fluorinated vinyl benzoic acid esters 2-3 may be treated with a metalhydroxide source such as lithium hydroxide in a mixed solvent systemcomprising a polar, aprotic solvent preferably tetrahydrofuran andpolar, protic solvents preferably methanol and water at about ambienttemperature to provide fluorinated vinyl benzoic acids 2-4 (Scheme 2,step c).

Alternatively, halobenzoic acids 2-1 may be directly treated with avinyl borane source such as vinyltrifluoroborate or3-hydroxy-2,3-dimethylbutan-2-yl hydrogen vinylboronate in the presenceof a palladium catalyst such as 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride, and a base such as potassium carbonate, in apolar, aprotic solvent preferably dimethylsulfoxide at temperaturesranging from about 80° C. to about 140° C., to provide vinyl benzoicacids 3-1, wherein R⁹, R¹⁰, R¹¹, and R¹² are as previously disclosed(Scheme 3, step a). Vinyl benzoic acids 3-1 may be treated with abromine source such as N-bromosuccinimide, and a fluorine source such astriethylamine trihydrofluoride, in a polar, aprotic solvent preferablydichloromethane at about 0° C., to provide bromofluoroalkyl benzoicacids 3-2, wherein R⁹, R¹⁰, R¹¹, and R¹² are as previously disclosed(Scheme 3, step b). Bromofluoroalkyl benzoic acids 3-2 may be treatedwith a base such as potassium tert-butoxide, in a polar, protic solventpreferably methanol, at temperatures ranging from about 0° C. to aboutambient temperature, to provide fluorinated vinyl benzoic acids 2-4(Scheme 3, step c).

Preparation of Fluorinated Phenyl Allylbenzoic Acids

Benzyl halides 1-4 and fluorinated vinylbenzoic acids 2-4 may be treatedwith a copper(I) source such as copper(I) chloride or copper(I) bromideand a pyridine ligand such as 2,2-bipyridyl in a polar, aprotic solventpreferably N-methyl-2-pyrrolidone, at a temperature between about 100°C. to about 180° C. to provide fluorinated phenyl allylbenzoic acids4-1, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, and R¹² are aspreviously disclosed (Scheme 4, step a).

Preparation of Diacylamines

Diacylamines 5-3, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹²,L, R¹³, R¹⁴, X, n, and R¹⁵ are as previously disclosed, may be preparedby treatment with acylamino salts 5-2, wherein L, R¹³, R¹⁴, X, n, andR¹⁵ are as previously disclosed, and activated carboxylic acids 5-1,wherein A is an activating group, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹,R¹⁰, R¹¹, and R¹² are as previously disclosed, with a base, such aspotassium bicarbonate, triethylamine, diisopropylethylamine, orpreferably 4-methylmorpholine in an anhydrous aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichioroethane,N,N-dimethylformamide, or any combination thereof, at temperaturesbetween about 0° C. and about 120° C. (Scheme 5, step a).

Activated carboxylic acids 5-1 may be an acid halide such as an acidchloride, an acid bromide, or an acid fluoride; a carboxylic ester suchas a para-nitrophenyl ester, a pentafluorophenyl ester, an ethyl(hydroxyimino)cyanoacetate ester, a methyl ester, an ethyl ester, abenzyl ester, an N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-ylester, or a hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acidanhydride; or a thioester. Acid chlorides may be prepared from thecorresponding carboxylic acids by treatment with a dehydrating,chlorinating reagent such as oxalyl chloride or thionyl chloride.Activated carboxylic acids 5-1 may be prepared from carboxylic acids insitu with a uronium salt such as1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU), or(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholine-carbeniumhexafluorophosphate (COMU). Activated carboxylic esters 5-1 may also beprepared from carboxylic acids in situ with a phosphonium salt such asbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBop). Activated carboxylic acids 5-1 may also be prepared fromcarboxylic acids in situ with a coupling reagent such as1-(3-dimethylamino propyl)-3-ethylcarbodiimide (EDC), ordicyclohexylcarbodiimide (DCC) in the presence of a triazole such ashydroxybenzotriazole•monohydrate (HOBt) or 1-hydroxy-7-azabenzotriazole(HOAt). O-Acylisoureas may be prepared with a dehydrating carbodimidesuch as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide ordicyclohexylcarbodiimide. Activated carboxylic acids 5-1 may also beprepared from carboxylic acids in situ with a coupling reagent such as2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in thepresence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt).

Diacylamines 5-3, wherein R¹⁵ contains a sulfide may be oxidized to thecorresponding sulfoxide and sulfone by treatment with one equivalent ofsodium perborate in a protic solvent such as acetic acid (sulfoxide) ortwo equivalents of sodium perborate (sulfone). Preferably, the oxidationwill be performed at temperatures between about 40° C. to about 100° C.using 1.5 equivalents of sodium perborate to provide chromatographicallyseparable mixtures of sulfoxide and sulfone diacylaminals 5-3, whereinR¹⁵ contains a sulfoxide or sulfone.

Diacylamines 5-3 may also be prepared by treatment of acylamine salts6-1, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, L andR¹⁴ are as previously disclosed, with activated coupling partners 6-2,wherein A is an activated group, and X, n, and R¹⁵ are as previouslydisclosed, with a base, such as potassium bicarbonate, triethylamine,diisopropylethylamine, or preferably 4-methylmorpholine in a polar,aprotic solvent such as dichloromethane, tetrahydrofuran,1,2-dichloroethane, N,N-dimethylformamide, or any combination thereof,at temperatures between about 0° C. and about 120° C. (Scheme 6, stepa).

Activated coupling partners 6-2, wherein A is an activated group,wherein X is C, n is 1, and R¹⁵ is as previously disclosed, may be anacid halide, such as an acid chloride, an acid bromide, or an acidfluoride; a carboxylic ester, such as a para-nitrophenyl ester, apentafluorophenyl ester, an ethyl (hydroxyimino)cyanoacetate ester, amethyl ester, an ethyl ester, a benzyl ester, a N-hydroxysuccinimidylester, a hydroxybenzotriazol-1-yl ester, or a hydroxypyridyltriazol-1-ylester; an O-acylisourea; an acid anhydride; or a thioester. Acidchlorides may be prepared from the corresponding carboxylic acids bytreatment with a dehydrating, chlorinating reagent such as oxalylchloride or thionyl chloride. Activated coupling partners 6-2 that areactivated carboxylic esters may be prepared from carboxylic acids insitu with a uronium salt such as1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(H BTU), or(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (COMU). Activated coupling partners 6-2 that areactivated carboxylic esters may also be prepared from carboxylic acidsin situ with a phosphonium salt such asbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBop). Activated coupling partners 6-2 that are activated carboxylicesters may also be prepared from carboxylic acids in situ with acoupling reagent such as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide(EDC), or dicyclohexylcarbodiimide (DCC) in the presence of a triazolesuch as hydroxybenzotriazole•monohydrate (HOBO or1-hydroxy-7-azabenzotriazole (HOAt). O-Acylisoureas may be prepared witha dehydrating carbodimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activatedcoupling partners 6-2 that are activated carboxylic esters may also beprepared from carboxylic acids in situ with a coupling reagent such as2-chloro-1,3-dirnethylimidazolidinium hexafluorophosphate (CIP) in thepresence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt).

Activated coupling partners 6-2, wherein A is an activated group,wherein X is P(C₁-C₄)alkyl, n is 1, and R¹⁵ is as previously disclosed,may be a phosphinic halide, such as a phosphinic chloride. Activatedcoupling partners 6-2, wherein A is an activated group, wherein X is S,n is 2, and R¹⁵ is as previously disclosed, may be a sulfonyl halide,such as a sulfonyl chloride.

Precursors to and activated coupling partners 6-2, wherein R¹⁵ containsa sulfide may be oxidized to the corresponding sulfoxide or sulfone bytreatment with one equivalent of sodium perborate in a protic solventsuch as acetic acid (sulfoxide) or two equivalents of sodium perborate(sulfone). Preferably, the oxidation will be performed at temperaturesbetween about 40° C. to about 100° C. using 1.5 equivalents of sodiumperborate to provide chromatographically separable mixtures of sulfoxideand sulfone precursors to and activated coupling partners 6-2,containing a sulfoxide or sulfone.

Diacylamines 7-2, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹²,L, R¹³, R¹⁴, and R¹⁵ are as previously disclosed, may also be preparedby treatment of acylamine salts 6-1 with isocyanates 7-1, wherein R¹⁵ isas previously disclosed, with a base, such as potassium bicarbonate,triethylamine, diisopropylethylamine, 4-methylmorpholine, or2,6-dimethylpyridne in a polar, aprotic solvent such as dichloromethane,tetrahydrofuran, 1,2-dichloroethane, N,N-dimethylformamide, pyridine, orany combination thereof, at temperatures between about 0° C. and about120° C., heated conventionally or by microwave (Scheme 7, step a).

Diacylamines 5-3 may be prepared by treating acylamines 8-1, wherein R¹⁴is H, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², L, X, n, andR¹⁵ are as previously disclosed, with an alkylating reagent R¹⁴—Z,wherein R¹⁴ is not H and is as previously disclosed, and Z is a leavinggroup, such as a halogen or a sulfonate, wherein R¹⁴—Z is an alkylhalide, such as iodomethane, or an activated alcohol, such asethyltriflate in the presence of a base, such as sodium hydride, cesiumcarbonate, silver oxide, potassium hydride, tetrabutylammonium fluoride,or potassium carbonate in a polar, aprotic solvent such asN,N-dimethylformamide, tetrahydrofuran, acetone, acetonitrile,dimethylsulfoxide, or glyme. Alternatively, the alkylation of acylamines8-1 may be conducted in a biphasic manner using an alkali metalhydroxide base, such as sodium hydroxide, in water, a phase-transfercatalyst, such as a tetraalkylammonium salt, in an organic solvent suchas toluene or dichloromethane at temperatures ranging from about 0° C.and about 120° C. (Scheme 8, step a).

Preparation of Acylamine Salt Precursors

Amides 9-2, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³,and L are as previously disclosed, are novel intermediates which may beused in the preparation of acylamine salts 6-1. Amides 9-2 may beprepared by reacting alpha-amino amides 9-1, wherein R¹³ and L are aspreviously disclosed, and an activated carboxylic acid 5-1 with a base,such as potassium bicarbonate, triethylamine, diisopropylethylamine, orpreferably 4-methylmorpholine in an polar, aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichloroethane,N,N-dimethylformamide, or any combination thereof, at temperaturesbetween about 0° C. and about 120° C. (Scheme 9, step a).

Preparation of Acylamine Salts

Acylamines 6-1, wherein R¹⁴ is H, may be prepared from amides 9-2 byconversion of the primary amide nitrogen to a nitrene-like species,resulting in nitrogen migration, followed by isocyanate formation.Hydrolysis of the intermediate isocyanate with aqueous acid, such ashydrochloric acid may provide acylamine salts 6-1 (Scheme 10, step a).When an acid weaker than aqueous hydrochloric acid is employed, anionexchange may be achieved by treatment with hydrochloric acid to provideacylamine salts 6-1. Preferably amide 9-2 may be treated withiodobenzene bis(trifluoroacetate) in a solvent mixture consisting ofabout two parts acetonitrile and about one part deionized water attemperatures between about 0° C. and about 120° C. The resultingtrifluoroacetate salt may be converted to the chloride salt by theaddition of hydrochloric acid followed by evaporation of volatiles.

Preparation of Acylamine Salts

Acylamine salts 10-3, wherein R¹⁴ and R¹⁵ are as previously disclosed,may be prepared according to those reactions outlined in Scheme 11,Scheme 12, and Scheme 13. Treatment of carboxylic acids 10-1, wherein Ais OH, R¹⁴, R¹⁵, and L are as previously disclosed, or the correspondingactivated acids 10-1, wherein A is an activating group as previouslydescribed may be reacted with a nitrogen nucleophile to provide amidesand amide derivatives 10-2, wherein Z² is H, N₂, NH tert-butoxycarbonyl,or OH, R¹⁴, R¹⁵, and L are as previously disclosed. The resultant amidesand amide derivatives 10-2 may be converted to acylamine salts 10-3 bythe formation of the corresponding nitrene-like species, resulting innitrogen migration, and subsequent hydrolysis of the resultantisocyanate.

Activated amido acids 10-1 may be treated with ammonia (Scheme 11, stepa) to provide carboxamides 10-2, wherein Z² is H. Carboxamides 10-2,wherein Z² is H, may be converted to acylamines 10-3 via the Hoffmanrearrangement followed by acidification with hydrochloric acid orpreferably by treatment with iodobenzene bis(trifluoroacetate) in asolvent mixture consisting of about one part acetonitrile and about onepart deionized water at temperatures between about 0° C. and about 120°C. (Scheme 11, step e). The resulting trifluoroacetate salt may beconverted to the chloride salt by the addition of hydrochloric acidfollowed by the evaporation of volatiles. Amido acids 10-1, wherein A isOH, may be treated with an azide source such as diphenylphosphoryl azidein the presence of a base, such as proton sponge or triethylamine(Scheme 11, step b) to provide acyl azides 10-2, wherein Z² is N₂.Alternatively, amido acids 10-1, wherein A is an activating group asdescribed above, may be treated with an azide source, such as sodiumazide (Scheme 11, step b) to provide acyl azides 10-2, wherein Z² is N₂.Acyl azides 10-2, may be heated to about 40° C. to about 110° C. in apolar, aprotic solvent, such as acetonitrile, toluene,1,2-dichloroethane, tetrahyrofuran, or 1,4-dioxane to affect a Curtiusrearrangement resulting in the formation of a non-isolated isocyanatethat may be treated with aqueous hydrochloric acid to provide acylaminesalts 5-2. Alternatively, the isocyanate may be treated with an alcohol,such as tert-butanol, para-methoxybenzyl alcohol, or benzyl alcohol toprovide an acid labile carbamate, which after purification may bedecomposed under acidic conditions to provide acylamine salts 10-3(Scheme 11, step f).

Activated amido acids 10-1 may be treated with protected hydrazines(Scheme 11, step c), such as tert-butyl carbazate in the presence of abase, such as 4-methylmorpholine, to provide protected hydrazides 10-2,wherein Z² is NHtert-butoxycarbonyl. Protected hydrazides 10-2 may bedeprotected by treatment with acids such as hydrochloric acid ortrifluoroacetic acid in aprotic solvents such as 1,4-dioxane ordichloromethane. The resulting hydrazide salts 10-2, wherein Z² isNH₃Cl, may be neutralized to provide hydrazide 10-2, wherein Z² is NH₂.Hydrazides 10-2 may then be diazotized with reagents such as nitric acidor isobutyl nitrite to produce isocyanates that may be converted toacylamine salts 10-3 (Scheme 11, step g).

Activated amido acids 10-1 are as previously disclosed, may be treatedwith hydroxylamine (Scheme 11, step d) to provide hydroxamic acids 10-2,wherein Z² is OH. Hydroxamic acids 10-2 may be acylated with activatedcarboxylic acids, wherein activated carboxylic acids are as previouslydisclosed, to provide the O-acyl hydroxamic acids 10-2, wherein Z² isO-acyl, which may be converted to isocyanates by treatment with heat orthe addition of base to produce isocyanates that may be converted toacylamine salts 10-3 (Scheme 11, step h).

Carbamate acids 11-1, wherein R¹⁴ is H and L is as previously disclosed,may be treated with an alkylating reagent R¹⁴—Z, wherein R¹⁴ is not Hand is as previously disclosed and Z is a leaving group, such as ahalogen or sulfonate, wherein R¹⁴—Z is an alkyl halide, such asiodomethane, or an activated alcohol, such as ethyltriflate, in thepresence of a base, such as sodium hydride, cesium carbonate, silveroxide, potassium hydride, tetrabutylammonium fluoride, or potassiumcarbonate in a polar, aprotic solvent such as N,N-dimethylformamide,tetrahydrofuran, acetone, acetonitrile, dimethylsulfoxide, or glyme.Alternatively, the alkylation of carbamate acids 11-1 may be conductedin a biphasic manner using an alkali metal hydroxide base, such assodium hydroxide, in water, a phase-transfer catalyst, such as atetraalkylammonium salt, in an organic solvent such as toluene ordichloromethane at temperatures ranging from about 0° C. to about 120°C. (Scheme 12, step a).

The resultant carbamate acids 11-2, wherein R¹⁴ and L are as previouslydisclosed, may be treated with an azide source such asdiphenylphosphoryl azide in the presence of a base, such as protonsponge or triethylamine (Scheme 12 step b) to provide an acyl azidewhich may in turn be heated from about 40° C. to about 110° C. in apolar, aprotic solvent, such as acetonitrile, toluene,1,2-dichioroethane, tetrahydrofuran, or 1,4-dioxane to affect a Curtiusrearrangement resulting in the formation of an isocyanate (Scheme 12,step c). Treatment of the resultant isocyanate with benzyl alcohol mayprovide a differentially protected diamine (Scheme 12, step d). Removalof the tert-butylcarbamate may be achieved by treatment with an acid,such as hydrochloric acid or trifluoroacetic acid, in a polar, aproticsolvent, such as 1,4-dioxane or dichloromethane, at temperatures betweenabout 0° C. and about 65° C., to provide benzyl carbamate amine salts11-3, wherein R¹⁴ and L are as previously disclosed (Scheme 12, step e).

Benzyl carbamate amine salts 11-3 may be treated with activatedcarboxylic acids 6-2, wherein X is C, in the presence of a base, such aspotassium bicarbonate, triethylamine, diisopropylethylamine, orpreferably 4-methylmorpholine in a polar, aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichloroethane,N,N-dimethylformamide, or any combination thereof, at temperaturesbetween about 0° C. and about 120° C. (Scheme 12, step f). The resultantcarbamate acylamine may be treated with a source of hydrogen and atransition metal catalyst, such as palladium on carbon to provideacylamine salts 10-3 (Scheme 12, step g).

Carbamate acids 11-1 may be treated with an alkylating reagent R¹⁶—Z,wherein R¹⁶ is (C₁-C₈)alkenyl and Z is a leaving group, such as ahalogen or a sulfonate, wherein R¹⁶—Z is an alkenyl halide, such asallyl bromide, or an activated alcohol, such as crotyltriflate in thepresence of a base, such as sodium hydride, cesium carbonate, silveroxide, potassium hydride, tetrabutylammonium fluoride, or potassiumcarbonate in a polar, aprotic solvent such as N,N-dimethylformamide,tetrahydrofuran, acetone, acetonitrile, dimethylsulfoxide, or glyme.Alternatively, the alkylation of carbamate acids 11-1 may be conductedin a biphasic system using an alkali metal hydroxide base, such assodium hydroxide, in water, a phase-transfer catalyst, such as atetraalkylammonium salt, in an organic solvent such as toluene ordichloromethane at temperatures ranging from about 0° C. to about 100°C. (Scheme 13, step a).

The resultant carbamate acids 12-1, wherein R¹⁶ and L are as previouslydisclosed, may be treated with an azide source such asdiphenylphosphoryl azide in the presence of a base, such as protonsponge or triethylamine (Scheme 13, step b) to provide an acyl azidewhich may in turn be heated to about 40° C. to about 110° C. in anaprotic solvent, such as acetonitrile, toluene, 1,2-dichloroethane,tetrahydrofuran, or 1,4-dioxane to affect a Curtius rearrangementresulting in the formation of an isocyanate (Scheme 13, step c).Treatment of the resultant isocyanate with benzyl alcohol may provide adifferentially protected diamine (Scheme 13, step d). Removal of thetert-butylcarbamate may be achieved by treatment with an acid, such ashydrochloric acid or trifluoroacetic acid, in a polar, aprotic solvent,such as 1,4-dioxane or dichloromethane, at temperatures between about 0°C. and about 65° C., to provide benzyl carbamate aminal salts 12-2,wherein R¹⁶ and L are as previously disclosed (Scheme 13, step e).

Benzyl carbamate amine salts 11-3 may be treated with activatedcarboxylic acids 10-3 in the presence of a base, such as potassiumbicarbonate, triethylamine, diisopropylethylamine, or preferably4-methylmorpholine in an anhydrous, aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichloroethane,N,N-dimethylformamide, or any combination thereof, at temperaturesbetween about 0° C. and about 120° C. (Scheme 13, step f). The resultantcarbamate acylaminal may be treated with a source of hydrogen and atransition metal catalyst, such as palladium on carbon to provideacylamine salts 10-3 (Scheme 13, step g).

Preparation of Amido Acids

Esters 13-2, wherein A is O(C₁-C₈)alkyl or O(C₁-C₈)alkylphenyl, and L,X, n, and R¹⁵ are as previously disclosed may be prepared by treatingamino esters 13-1, wherein A is O(C₁-C₈)alkyl or O(C₁-C₈)alkylphenyl,and L is as previously disclosed, with activated coupling partners 6-2,a base, such as potassium bicarbonate, triethylamine,diisopropylethylamine, or preferably 4-methylmorpholine in an anhydrous,aprotic solvent such as dichloromethane, tetrahydrofuran,1,2-dichloroethane, N,N-dimethylformamide, or any combination thereof,at temperatures between about 0° C. and about 120° C. (Scheme 14, stepa).

Esters 13-2 may be treated with an alkylating reagent R¹⁴—Z, wherein R¹⁴is not H and is as previously disclosed, and Z is a leaving group, suchas a halogen or a sulfonate, wherein R¹⁴—Z is an alkyl halide, such asiodomethane or an activated alcohol, such as ethyltriflate in thepresence of a base, such as sodium hydride, cesium carbonate, silveroxide, potassium hydride, tetrabutylammonium fluoride, or potassiumcarbonate in a polar, aprotic solvent such as N,N-dimethylformamide,tetrahydrofuran, acetone, acetonitrile, dimethylsulfoxide, or glyme.Alternatively, the alkylation of esters 13-2 may be conducted in abiphasic system using an alkali metal hydroxide base, such as sodiumhydroxide, in water, a phase-transfer catalyst, such as atetraalkylammonium salt, in an organic solvent such as toluene ordichloromethane at temperatures ranging from about 0° C. to about 120°C. (Scheme 14, step b).

The resultant alkylated esters, when A is O(C₁-C₈)alkyl, may be treatedwith an acid, such as aqueous hydrochloric acid, in a polar, aproticsolvent, such as 1,4-dioxane, at about 100° C. to provide acids 13-4,wherein L, R¹⁴, X, n, and R¹⁵ are as previously disclosed.Alternatively, alkylated esters, when A is O-tea-butyl, may be treatedwith hydrochloric acid in 1,4-dioxane. Alkylated esters, when A isO(C₁-C₈)alkyl may be treated with an alkali base, such as lithiumhydroxide, in a polar solvent, such as 1,4-dioxane, tetrahydrofuran,methanol, water, or mixtures thereof, at temperatures between 0° C. andabout 140° C. to provide acids 13-4. The alkylated esters, when A isO(C₁-C₈)alkylphenyl may be treated with a source of hydrogen and atransition metal catalyst, such as palladium on carbon to provide acids13-4 (Scheme 14, step c).

Acids 13-4 may be prepared in alternate sequences to the sequencediscussed above. Step b may be initially performed to providesubstituted esters 13-3, wherein A is O(C₁-C₈)alkyl orO(C₁-C₈)alkylphenyl, and R¹⁴ and L are as previously disclosed, beforesteps a and steps c are performed to provide acids 13-4.

Substituted esters 13-3 may be prepared by treating esters 13-1 withR¹⁶—C(O)H or R¹⁶—C(O)(C₁-C₈)alkyl, wherein R¹⁶ is not H, in the presenceof a reductant, such as sodium borohydride or sodium cyanoborohydride,in protic solvents such as methanol or ethanol in the presence of weakorganic acids, such as acetic acid. Alternatively, the imineintermediate resulting from condensation of the amine and the carbonylmay be reduced by a source of hydrogen and a transition metal catalyst,such as palladium on carbon to provide substituted esters 13-3, when Ais O(C₁-C₅)alkyl (Scheme 14, step d).

Acids 13-4 may be prepared in a two-step sequence, by first treatingsubstituted esters 13-3 with activated coupling partners 6-2, with abase, such as potassium bicarbonate, triethylamine,diisopropylethylamine, or preferably 4-methylmorpholine in an anhydrousaprotic solvent such as dichloromethane, tetrahydrofuran,1,2-dichloroethane, N,N-dimethylformamide, or any combination thereof,at temperatures between about 0° C. and about 120° C. (Scheme 14, stepe).

Secondly, the resultant esters, when A is O(C₁-C₈)alkyl may be treatedwith an acid, such as aqueous hydrochloric acid, in a polar, aproticsolvent, such as 1,4-dioxane, at about 100° C. to provide amido acids13-4. Alternatively, esters, when A is Otert-butyl, may be treated withhydrochloric acid in 1,4-dioxane. Esters, when A is O(C₁-C₈)alkyl may betreated with an alkali base, such as lithium hydroxide, in a polarsolvent, such as 1,4-dioxane, tetrahydrofuran, methanol, water, ormixtures thereof, at temperatures between 0° C. and about 100° C. toprovide acids 13-4. Finally, acylated esters, when A isO(C₁-C₈)alkylphenyl may be treated with a source of hydrogen and atransition metal catalyst, such as palladium on carbon to provide acids13-4 (Scheme 14, step f).

Acids 13-2 may be prepared by treating amino esters 13-1 with activatedcoupling partners 6-2, a base, such as potassium bicarbonate,triethylamine, diisopropylethylamine, or preferably 4-methylmorpholinein an anhydrous, aprotic solvent such as dichloromethane,tetrahydrofuran, 1,2-dichloroethane, N,N-dimethylformamide, or anycombination thereof, at temperatures between about 0° C. and about 120°C. (Scheme 14, step a).

Esters 13-2 may be treated with an alkylating reagent R¹⁶—Z, wherein R¹⁶is (C₁-C₈)alkenyl and Z is a leaving group, such as a halogen or asulfonate, wherein R¹⁶—Z is an alkyl halide, such as allyl bromide, oran activated alcohol, such as crotyltriflate in the presence of a base,such as sodium hydride, cesium carbonate, silver oxide, potassiumhydride, tetrabutylammonium fluoride, or potassium carbonate in a polar,aprotic solvent such as N,N-dimethylformamide, tetrahydrofuran, acetone,acetonitrile, dimethylsulfoxide, or glyme. Alternatively, the alkylationof esters 13-2 may be conducted in a biphasic system using an alkalimetal hydroxide base, such as sodium hydroxide, in water, aphase-transfer catalyst, such as a tetraalkylammonium salt, in anorganic solvent such as toluene or dichloromethane at temperaturesranging from about 0° C. to about 100° C. (Scheme 15, step b). Thealkene present in R¹⁶ may be subsequently reduced by a source ofhydrogen and a transition metal catalyst, such as palladium on carbon.In alkylated esters when A is O(C₁-C₈)alkylphenyl reduction of thealkene may also lead to concomitant reduction of the ester to provideamido acids 13-4 (Scheme 15, step c).

Alkylated amido esters, when A is O(C₁-C₈)alkyl may be treated with anacid, such as aqueous hydrochloric acid, in a polar, aprotic solvent,such as 1,4-dioxane, at about 100° C. to provide amido acids 13-4.Alternatively, esters, when A is Otert-butyl, may be treated withhydrochloric acid in 1,4-dioxane. Alkylated esters, when A isO(C₁-C₈)alkyl may be treated with an alkali base, such as lithiumhydroxide, in a polar solvent, such as 1,4-dioxane, tetrahydrofuran,methanol, water, or mixtures thereof, at temperatures between 0° C. andabout 100° C. to provide acids 13-4 (Scheme 15, step d).

Acids 13-4 may be prepared in alternate sequences to the sequencediscussed above. Step b may be initially performed to providesubstituted esters 13-1, wherein A is O(C₁-C₈)alkyl orO(C₁-C₈)alkylphenyl, and L and R¹⁵ are as previously disclosed, beforesteps a and steps c, or steps a, steps c, and steps d are performed toprovide 13-4.

EXAMPLES

These examples are for illustration purposes and are not to be construedas limiting this disclosure to only the embodiments disclosed in theseexamples.

Starting materials, reagents, and solvents that were obtained fromcommercial sources were used without further purification. Anhydroussolvents were purchased as Sure/Seal™ from Aldrich and were used asreceived. Melting points were obtained on a Thomas Hoover Unimeltcapillary melting point apparatus or an OptiMelt Automated Melting PointSystem from Stanford Research Systems and are uncorrected. Examplesusing “room temperature” were conducted in climate controlledlaboratories with temperatures ranging from about 20° C. to about 24° C.Molecules are given their known names, named according to namingprograms within ISIS Draw, ChemDraw, or ACD Name Pro. If such programsare unable to name a molecule, such molecule is named using conventionalnaming rules. ¹H NMR spectral data are in ppm (δ) and were recorded at300, 400, 500, or 600 MHz; ¹³C NMR spectral data are in ppm (δ) and wererecorded at 75, 100, or 150 MHz, and ¹⁹F NMR spectral data are in ppm(δ) and were recorded at 376 MHz, unless otherwise stated.

Example 1: Preparation of(Z)-2-bromo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C1)

To a 25 mL round-bottomed flask were added 2,2′-bipyridine (0.255 g,1.63 mmol), 2-bromo-4-(1-fluorovinyl)benzoic acid (C24) (1.00 g, 4.08mmol), and 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (2.79g, 8.16 mmol) in N-methylpyrrolidone (2.0 mL) to give a yellow solution.Copper(I) bromide (0.117 g, 0.816 mmol) was added and the reactionmixture was purged with nitrogen for 5 minutes. The reaction was thenheated to 150° C. for 3 hours. The reaction mixture was poured into icewater (100 mL). The water was filtered and the resultant black gum wasdissolved in ethyl acetate (800 mL), washed with brine (2×200 mL), andwater (2×200 mL), dried over magnesium sulfate, filtered, andconcentrated to provide the title compound as a brown oil (1.40 g, 64%):¹H NMR (400 MHz, CDCl₃) δ 8.03 (d, J=8.2 Hz, 1H), 7.89 (d, J=1.8 Hz,1H), 7.59 (dd, J=8.3, 1.8 Hz, 1H), 7.43 (s, 2H), 5.83 (dd, J=32.4, 9.6Hz, 1H), 4.60 (p, J=8.8 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−69.32 (d,J=2.3 Hz), −108.70-−119.01 (m); ESIMS m/z 505 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 1:

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2)

Isolated as a yellow oil (7.6 g, 68%): ¹H NMR (400 MHz, CDCl₃) δ 8.04(d, J=8.2 Hz, 1H), 7.99-7.94 (m, 1H), 7.84 (dd, J=8.2, 1.8 Hz, 1H), 7.44(s, 2H), 5.90 (dd, J=32.4, 9.6 Hz, 1H), 4.62 (p, J=8.9 Hz, 1H); ¹⁹F NMR(376 MHz, CDCl₃) δ−59.60, −69.28 (d, J=2.3 Hz), −112.11; ESIMS m/z 493([M−H]⁻).

(Z)-4-(1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C3)

Isolated as a yellow foam (0.628 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 8.00(d, J=8.2 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.42(s, 2H), 5.96 (dd, J=33.6, 9.8 Hz, 1H), 4.29 (td, J=14.3, 9.8 Hz, 1H),1.65 (t, J=18.4 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.61,−92.97-−97.35 (m), −114.82; ESIMS m/z 491 ([M−H]⁻).

(Z)-2-Chloro-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C4)

Isolated as a white solid (4.27 g, 88%): ¹H NMR (400 MHz, CDCl₃) δ 8.07(d, J=8.2 Hz, 1H), 7.68 (d, J=1.7 Hz, 1H), 7.54 (dd, J=1.8 Hz, 1H), 7.43(s, 2H), 5.85 (dd, J=32.4, 9.6 Hz, 1H), 4.60 (p, J=8.8 Hz, 1H); ¹⁹F NMR(376 MHz, CDCl₃) δ−69.33 (d, J=2.2 Hz), −112.18 (d, J=2.4 Hz); ESIMS m/z461 ([M−H]⁻).

(Z)-4-(3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C5)

Isolated as a brown gum (2.00 g, 37%): ESIMS m/z 583 ([M−H]⁻).

(Z)-4-(3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C6)

Isolated as a brown gum (0.50 g, 43%): ¹H NMR (400 MHz, DMSO-d₆) δ 13.9(br s, 1H), 8.16 (s, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.92 (d, J=8.0 Hz,1H), 7.82 (s, 2H), 7.64 (t, J=6.0 Hz, 1H), 6.90 (dd, J=36.0, 10.4 Hz,1H), 5.26-5.17 (m, 1H); IR (thin film) 3416, 2926, 1716, 1119 cm⁻¹;ESIMS m/z 449 ([M+H]⁺).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C7)

Isolated as a brown gum (2.50 g, 56%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.9(br s, 1H), 8.16 (s, 1H), 8.09 (d, J=10.8 Hz, 1H), 8.08 (s, 1H), 7.92(d, J=8.1 Hz, 1H), 7.75-7.65 (m, 2H), 6.90 (dd, J=36.0, 10.4 Hz, 1H),5.22-5.16 (m, 1H); IR (thin film) 3440, 2927, 1716, 1175 cm⁻¹; ESIMS m/z459 ([M−H]⁶⁻).

(Z)-4-(3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C8)

Isolated as a brown gum (2.20 g, 39%): ¹H NMR (300 MHz, CDCl₃) δ8.05-7.95 (m, 2H), 7.84 (d, J=7.2 Hz, 1H), 7.69-7.68 (m, 1H), 7.49 (s,2H), 5.95 (dd, J=32.7, 9.6 Hz, 1H), 4.64-4.58 (p, 1H); IR (thin film)3439, 2925, 1714, 1118, 746 cm⁻¹; ESIMS m/z 549 ([M−H]⁻).

(Z)-4-(3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C9)

Isolated as a brown gum (1.20 g, 54%): ¹H NMR (300 MHz, CDCl₃) δ 7.88(s, 2H), 7.76-7.75 (m, 1H), 7.37 (d, J=6.0 Hz, 2H), 5.90 (dd, J=32.1,9.0 Hz, 1H), 4.62-4.56 (p, 1H); IR (thin film) 3445, 2926, 1698, 1260,750 cm⁻¹; ESIMS m/z 477 ([M−H]⁻).

(Z)-4-(3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C10)

Isolated as a yellow gum (2.20 g, 53%): ¹H NMR (300 MHz, CDCl₃) δ 8.01(d, J=8.1 Hz, 1H), 7.94 (s, 1H), 7.83 (d, J=8.1 Hz, 1H), 7.11 (s, 2H),6.00 (dd, J=33.0, 9.9 Hz, 1H), 4.58-4.55 (m, 1H), 2.40 (s, 6H); IR (thinfilm) 3445, 1713, 852 cm⁻¹; ESIMS m/z 453 ([M−H]⁻),(Z)-4-(3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C11)

Isolated as a brown solid (1.50 g, 65%): mp 78-81° C.; ¹H NMR (300 MHz,CDCl₃) δ 8.09-7.99 (m, 2H), 7.83-7.81 (m, 1H), 7.42 (s, 2H), 5.95 (dd,J=32.4 Hz, 9.6 Hz, 1H), 4.63-4.57 (m, 1H); IR (thin film) 3445, 1713,852 cm⁻¹; ESIMS m/z 538 ([M+H]⁺).

(Z)-4-(3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C12)

Isolated as a brown gum (2.0 g, 62%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.80(br s, 1H), 8.15 (s, 1H), 8.09 (d, J=8.1 Hz, 1H), 7.93-7.78 (m, 4H),6.91 (dd, J=35.7, 10.2 Hz, 1H), 5.27-5.14 (m, 1H); IR (thin film) 3081,2927, 1714, 776 cm⁻¹; ESIMS m/z 503 ([M−H]⁻).

(Z)-4-(3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C13)

Isolated as a yellow gum (2.1 g, 78%): ¹H NMR (400 MHz, CDCl₃) δ 8.02(d, J=8.4 Hz, 1H), 7.94 (s, 1H), 7.83 (d, J=8.4 Hz, 1H), 7.66 (d, J=8.4Hz, 2H), 7.26-7.21 (m, 1H), 5.96 (dd, J=32.4, 9.2 Hz, 1H), 4.67-4.58 (p,1H); IR (thin film) 3426, 2925, 1714, 1115 cm⁻¹; ESIMS m/z 547 ([M−H]⁻).

(Z)-2-Methyl-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C14)

Isolated as an orange oil (0.94 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ 8.09(d, J=8.8 Hz, 1H), 7.49-7.45 (m, 2H), 7.44 (s, 2H), 5.80 (dd, J=32.7,9.6 Hz, 1H), 4.60 (p, J=8.9 Hz, 1H), 2.69 (s, 3H); ¹⁹F NMR (376 MHz,CDCl₃) δ−69.40 (d, J=2.3 Hz), −108.40-−115.65 (m); ESIMS m/z 441([M−H]⁻).

(Z)-2-Methyl-4-(1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)benzoicacid (C15)

Isolated as an orange foam (0.204 g, 51): ¹H NMR (400 MHz, CDCl₃) δ 8.07(d, J=8.8 Hz, 1H), 7.49-7.40 (m, 4H), 5.86 (dd, J=33.9, 9.9 Hz, 1H),4.27 (td, J=14.3, 9.7 Hz, 1H), 2.68 (s, 3H), 1.65 (t, J=18.4 Hz, 3H);¹⁹F NMR (376 MHz, CDCl₃) δ−95.11, −95.18, −114.57; ESIMS m/z 437([M−H]⁻).

(Z)-4-(1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)hex-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C16)

Isolated as an orange foam (0.136 g, 63%): ¹H NMR (400 MHz, CDCl₃) δ7.99 (dd, J=8.4, 4.0 Hz, 1H), 7.93 (s, 1H), 7.80 (d, J=7.9 Hz, 1H), 7.42(d, J=2.6 Hz, 2H), 6.08-5.87 (m, 1H), 4.32 (td, J=14.6, 9.8 Hz, 1H),1.87 (ddt, J=21.6, 15.4, 8.0 Hz, 2H), 1.07 (t, J=7.4 Hz, 3H); ¹³C NMR(101 MHz, CDCl₃) δ 170.72, 156.96 (d, J_(CF)=253.0 Hz), 136.85, 135.06,134.53, 133.75, 131.90, 131.19, 130.18, 129.17, 128.60, 128.05, 127.29,124.11, 123.36-122.67 (m), 121.39, 104.66 (d, J_(CF)=18.0 Hz), 46.46,29.70-27.14 (m), 6.40-5.44 (m); ESIMS m/z 503 ([M−H]⁻).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C17)

Isolated as an orange glass (0.495 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ8.01 (d, J=8.2 Hz, 1H), 7.94 (d, J=1.6 Hz, 1H), 7.80 (dd, J=8.2, 1.8 Hz,1H), 7.49 (d, J=2.1 Hz, 1H), 7.45 (d, J=8.3 Hz, 1H), 7.26 7.22 (m, 1H),6.00 (dd, J=33.9, 9.8 Hz, 1H), 4.32 (ddd, J=15.8, 13.0, 9.8 Hz, 1H),1.62 (t, J=18.4 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−59.58, −89.79-−99.81(m), −115.63; IR (thin film) 3008, 1711 cm⁻¹; ESIMS m/z 455 ([M−H]⁻).

(Z)-4-(3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C18)

Isolated as a brown gum (2.5 g, 46%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.79(br s, 1H), 8.15-8.06 (m, 3H), 7.91 (d, J=8.1 Hz, 1H), 7.71 (s, 2H),6.90 (dd, J=36.0, 10.2 Hz, 1H), 5.21-5.15 (m, 1H); IR (thin film) 3431,2924, 1623, 597 cm⁻¹; ESIMS m/z 503 ([M−H]⁻).

(Z)-4-(3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C19)

Isolated as a yellow gum (1.50 g, 57%): ¹H NMR (300 MHz, CDCl₃) δ 8.01(d, =8.1 Hz, 2H) 7.94 (s, 2H), 7.76-7.75 (m, 1H), 7.37 (d, J=6.0 Hz,2H), 5.90 (dd, J=32.1, 9.0 Hz, 1H); IR (thin film) 3445, 2926, 1698,1260, 750 cm⁻¹; ESIMS m/z 443 ([M−H]⁻).

(Z)-4-(3-(4-Chloro-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C20)

Isolated as a brown gum (0.50 g, 48%): ¹H NMR (300 MHz, CDCl₃) δ 8.03(d, J=8.1 Hz, 1H), 7.94 (s, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.46-7.44 (m,1H), 7.23-7.13 (m, 2H), 5.98 (dd, J=34.2, 9.9 Hz, 1H), 4.69-4.63 (m,1H); IR (thin film) 3092, 1751, 750 cm⁻¹; ESIMS m/z 443 ([M−H]⁻).

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (CC1)

Isolated as a yellow gum (1.1 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 8.15(d, J=8.2 Hz, 2H), 7.67 (d, J=8.3 Hz, 2H), 7.44 (s, 2H), 5.84 (dd,J=32.6, 9.6 Hz, 1H), 4.61 (p, J=8.9 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃)δ−69.38 (d, J=2.2 Hz), −109.75-−116.47 (m); ESIMS m/z 427 ([M−H]⁻).

Example 2: Preparation of(Z)-2-iodo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C21)

To a 25 mL vial were added(Z)-2-bromo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C1) (0.500 g, 0.987 mmol), copper(I) iodide (0.00940 g, 0.0490mmol), and 1,4-dioxane (4.9 mL) to form a yellow suspension. Sodiumiodide (0.296 g, 1.97 mmol) andtrans-N,N′-dimethylcyclohexane-1,2-diamine (0.0140 g, 0.0990 mmol) wereadded, and the reaction mixture was stirred at 110° C. for 3.5 hours.The reaction mixture was concentrated and purified by flash columnchromatography to provide the title compound as a brown oil (0.247 g,43%): ¹H NMR (300 MHz, CDCl₃) δ 8.21 (d, J=1.7 Hz, 1H), 8.02 (d, J=8.2Hz, 1H), 7.62 (dd, J=8.3, 1.7 Hz, 1H), 7.43 (s, 2H), 5.82 (dd, J=32.5,9.6 Hz, 1H), 4.59 (p, J=8.9 Hz, 1H); ¹⁹F NMR (471 MHz, CDCl₃) δ−69.32,−112.14 (d, J=20.8 Hz); ESIMS m/z 553 ([M−H]⁻).

Example 3: Preparation of(Z)-2-iodo-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C22)

Tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.26 mmol) was addedto a solution of(Z)-4-(3-(4-bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C11) (1.4 g, 2.6 mmol) in toluene (10 mL) at room temperature. Thereaction mixture was degassed by purging with nitrogen (3×10 minutes).Tributyl vinyl stannane (0.82 g, 2.6 mmol) was added to the reactionmixture. The reaction mixture was again degassed by purging withnitrogen (3×10 minutes) and stirred at 120° C. for 3 hours. The reactionmixture was quenched with water and then extracted with ethyl acetate.The organic layer was dried over sodium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 30%ethyl acetate/hexanes provided the title compound as a pale yellow gum(0.80 g, 63%); ¹H NMR (300 MHz, CDCl₃) δ 7.85 (s, 1H), 7.82 (d, J=8.4Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.42 (s, 1H), 7.37 (s, 1H), 6.72-6.65(dd, J=17.6 Hz, 11.6 Hz, 1H), 5.86-5.73 (m, 3H), 4.61-4.56 (m, 1H); IR(thin film) 3445, 2925, 1646, 1275, 749 cm⁻¹; ESIMS m/z 488 ([M+H]⁺).

Example 4: Preparation of(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoylchloride (C23)

To a 25 mL vial was added(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2) (0.200 g, 0.404 mmol), oxalyl chloride (0.095 mL, 1.09 mmol),and N,N-dirnethylformamide (catalytic amount) in dichloromethane (1.3mL) to give a yellow solution. The reaction was stirred for 15 hours atroom temperature. The solvent was removed under vacuum providing thetitle compound as a yellow gum (0.220 g, 95%): ¹H NMR (400 MHz, CDCl₃) δ7.99 (d, J=8.2 Hz, 1H), 7.92 (d, J=1.7 Hz, 1H), 7.81 (dd, J=8.2, 1.8 Hz,1H), 7.44 (5, 2H), 5.88 (dd, J=32.5, 9.6 Hz, 1H), 4.73-4.50 (m, 1H); ¹⁹FNMR (376 MHz, CDCl₃) δ−59.58, −69.32, −109.75-−113.19 (m); IR (thinfilm) 3445, 2925, 1646, 1275, 749 cm⁻¹; ESIMS m/z 476 ([M−Cl]⁺).

Example 5: Preparation of 2-bromo-4-(1-fluorovinyl)benzoic acid (C24)

To a 250 mL round-bottomed flask were added methyl2-bromo-4-(1-fluorovinyl)benzoate (C29) (1.8 g, 7.0 mmol), lithiumhydroxide hydrate (0.88 g, 21 mmol), methanol (7.0 mL), tetrahydrofuran(21 mL), and water (7.0 mL), and the reaction mixture was stirredovernight at room temperature. The mixture was concentrated, quenchedwith a pH 4 buffer, and extracted with ethyl acetate to provide thetitle compound as a white solid (1.0 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ8.01 (d, J=8.2 Hz, 1H), 7.89 (d, J=1.8 Hz, 1H), 7.57 (dd, J=8.3, 1.8 Hz,1H), 5.21 (dd, J=48.6, 4.0 Hz, 1H), 5.06 (dd, J=17.3, 3.9 Hz, 1H); ¹⁹FNMR (471 MHz, CDCl₃) δ−108.71 (d, J=1.4 Hz); ESIMS m/z 244 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 5:

4-(1-Fluorovinyl)-2-(trifluoromethyl)benzoic acid (C25)

Isolated as a white solid (1.9 g, 93%): ¹H NMR (400 MHz, methanol-d₄) δ7.95 (d, J=1.5 Hz, 1H), 7.95-7.91 (m, 1H), 7.90-7.86 (m, 1H), 5.46 (dd,J=50.0, 4.1 Hz, 1H), 5.09 (dd, J=18.0, 4.1 Hz, 1H); ¹⁹F NMR (376 MHz,methanol-d₄) δ−61.04 (d, J=1.1 Hz), −110.93; ESIMS m/z 233 ([M−H]⁻).

2-Chloro-4-(1-fluorovinyl)benzoic acid (C26)

Isolated as a white solid (3.5 g, 75%): ¹H NMR (400 MHz, acetone-d₆) δ7.97 (dd, J=8.2, 0.9 Hz, 1H), 7.76 (d, J=1.7 Hz, 1H), 7.70 (dd, J=8.2,1.7 Hz, 1H), 5.68-5.45 (m, 1H), 5.11 (dd, J=18.2, 4.1 Hz, 1H); ¹⁹F NMR(376 MHz, acetone-d₆) δ−108.71; ESIMS m/z 200 ([M−H]⁻).

4-(1-Fluorovinyl)-2-methylbenzoic acid (C27)

Isolated as a white solid (0.550 g, 89%): ¹H NMR (400 MHz, methanol-d₄)δ 7.92 (d, J=8.1 Hz, 1H), 7.59-7.52 (m, 1H), 7.52-7.44 (m, 1H), 5.29(dd, J=50.1, 3.7 Hz, 1H), 4.93 (dd, J=18.1, 3.7 Hz, 1H), 2.60 (s, 3H);¹⁹F NMR (376 MHz, methanol-d₄) δ−110.32 (d, J=2.1 Hz); ESIMS m/z 181([M+H]⁺).

Example 6: Preparation of methyl4-(1-fluorovinyl)-2-(trifluoromethyl)benzoate (C28)

To a 100 mL round-bottomed flask was added methyl4-bromo-2-(trifluoromethyl)benzoate (2.25 g, 8.00 mmol),fluorovinyl)(methyl)diphenylsilane (3.58 g, 14.8 mmol), and1,3-dimethylimidazolidin-2-one (40 mL).Tetrakis(triphenylphosphine)palladium(0) (0.459 g, 0.400 mmol),copper(I) iodide (0.0760 mg, 0.400 mmol), and cesium fluoride (3.62 g,23.9 mmol) were added and the reaction was stirred at room temperaturefor 24 hours under a nitrogen atmosphere. Water was added to the mixtureand the mixture was diluted with 3:1 hexanes/diethyl ether. The layerwas separated, and the organic layer was dried over sodium sulfate,concentrated, and the residue was purified by flash columnchromatography provided the title compound as a colorless oil (2.00 g,96%): ¹H NMR (400 MHz, CDCl₃) δ 7.96-7.87 (m, 1H), 7.83 (dq, J=8.1, 0.7Hz, 1H), 7.77 (dd, J=8.2, 1.7 Hz, 1H), 5.23 (dd, J=48.6, 4.0 Hz, 1H),5.07 (dd, J=17.4, 4.0 Hz, 1H), 3.95 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃)δ−59.92, −108.73 (d, J=1.4 Hz); EIMS m/z 248 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 6:

Methyl 2-bromo-4-(1-fluorovinyl)benzoate (C29)

Isolated as a colorless oil (1.8 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ 7.84(d, J=1.7 Hz, 1H), 7.82 (dd, J=8.2, 0.9 Hz, 1H), 7.50 (d, J=1.5 Hz, 1H),5.16 (dd, J=48.7, 3.9 Hz, 1H), 5.01 (dd, J=17.3, 3.9 Hz, 1H), 3.94 (d,J=2.2 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−108.61 (d, J=1.5 Hz); ESIMSm/z 258 ([M−H]⁻).

Methyl 2-chloro-4-(1-fluorovinyl)benzoate (C30)

Isolated as a colorless oil (2.1 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.86(dd, J=8.2, 0.9 Hz, 1H), 7.64 (d, J=1.7 Hz, 1H), 7.48 (dd, J=8, 3, 1.8Hz, 1H), 5.17 (dd, J=48.7, 3.8 Hz, 1H), 5.02 (dd, J=17.3, 3.9 Hz, 1H),3.94 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−108.63 (d, J=1.4 Hz); ESIMS m/z214 ([M−H]⁻).

Methyl 2-chloro-4-(1-fluorovinyl)benzoate (C31)

Isolated as a colorless oil (0.5 g, 85%): ¹H NMR (400 MHz, methanol-d₄)δ 7.90 (d, J=8.2 Hz, 1H), 7.51 (s, 1H), 7.49 (dd, J=8.0, 1.6 Hz, 1H),5.30 (dd, J=50.1, 3.7 Hz, 1H), 4.95 (dd, J=18.0, 3.7 Hz, 1H), 3.88 (d,J=5.9 Hz, 3H), 2.59 (s, 3H); ¹⁹F NMR (376 MHz, methanol-d₄) δ−110.41 (d,J=1.3 Hz); ESIMS m/z 195 ([M+H]⁺).

Example 7: Preparation of 4-(1-fluorovinyl)-2-(trifluoromethyl)benzoicacid (C25)

Step 1: 4-(2-bromo-1-fluoroethyl)-2-(trifluoromethyl)benzoic acid (C32)

2-(Trifluoromethyl)-4-vinylbenzoic acid (5.3 g, 24 mmol) was dissolvedin dichloromethane (123 mL) at 0° C., triethylamine trihydrofluoride wasadded (8.0 mL, 49 mmol) followed by N-bromosuccinimide (8.7 g, 49 mmol).The reaction mixture was stirred for 16 hours while warming to roomtemperature. Water was then added to the mixture, washed withdichloromethane, dried over sodium sulfate, filtered, and concentratedproviding the title compound as a yellow oil which was used withoutfurther purification (5.0 g, 65%).

Step 2: 4-(1-fluorovinyl)-2-(trifluoromethyl)benzoic acid (C25)

4-(2-Bromo-1-fluoroethyl)-2-(trifluoromethyl)benzoic acid (4.3 g, 14mmol) was dissolved in methanol (68 mL) at 0° C. and potassiumtert-butoxide (4.6 g, 41 mmol) was added as a solid while stirring. Thereaction mixture was allowed to slowly warm to 23° C. and then stirredfor 4 hours. Hydrochloric acid (1 N) was slowly added, and the mixturewas extracted with ethyl acetate. Purification by flash columnchromatography using 0-40% acetone/hexanes provided the title compoundas an off-white solid (1.7 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d,J=8.2 Hz, 1H), 8.00 7.93 (m, 1H), 7.82 (dd, J=8.2, 1.8 Hz, 1H), 5.27(dd, J=48.5, 4.1 Hz, 1H), 5.11 (dd, J=17.3, 4.1 Hz, 1H).

The following compounds were prepared in like manner to the procedureoutlined in Example 7:

4-(1-Fluorovinyl)benzoic acid (C33)

Isolated as a white solid (6.5 g, 86%): ¹H NMR (400 MHz, CDCl₃) δ 8.13(d, J=8.2 Hz, 2H), 7.69-7.62 (m, 2H), 5.21 (dd, J=49.0, 3.7 Hz, 1H),5.02 (dd, J=17.5, 3.7 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−108.35; ESIMSm/z 165 ([M−H]⁻).

4-(1-Fluorovinyl)-2-methylbenzoic acid (C27)

Isolated as a colorless oil (0.165 g, 89%): ¹H NMR (400 MHz, CDCl₃) δ8.12-8.03 (m, 1H), 7.46 (dd, J=5.8, 2.1 Hz, 2H), 5.17 (dd, =49.1, 3.7Hz, 1H), 4.98 (dd, J=17.5, 3.7 Hz, 1H), 2.68 (s, 3H); ¹⁹F NMR (376 MHz,CDCl₃) δ−108.50.

Example 8: Preparation of5-(1-bromo-2,2-difluoropropyl)-1,2,3-trichlorobenzene (C34)

N-bromosuccinimide (12.0 g, 67.5 mmol) was added to a solution of2,2-difluoro-1-(3,4,5-trichlorophenyl)propan-1-ol (C43) (6.00 g, 21.8mmol) in dichloromethane (72.6 mL). To this stirred solution was addedtriphenyl phosphite (17.1 mL, 65.3 mmol) slowly, dropwise, and thereaction mixture became dark brown. The reaction mixture was then heatedat reflux for 3 hours. The solvent was concentrated, and the residue wastriturated with diethyl ether. The solid was filtered, the filtrate wasconcentrated and the resultant oil was purified by flash columnchromatography using hexanes as eluent to provide the title compound asa clear and colorless oil (2.20 g, 25%): ¹H NMR (400 MHz, CDCl₃) δ 7.52(s, 2H), 4.85 (dd, J=12.3, 10.4 Hz, 1H), 1.77 (t, J=18.2 Hz, 3H); ¹⁹FNMR (376 MHz, CDCl₃) δ−92.14-−95.01 (m); EIMS m/z 338 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 8:

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)-2-chlorobenzene (C35)

Isolated as a clear oil (28 g, 56%): ¹H NMR (400 MHz, DMSO-d₆) δ8.01-7.97 (m, 2H), 6.26-6.20 (m, 1H); IR (thin film) 1168, 736, 557cm⁻¹; ESIMS m/z 428 ([M+H]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1,3-dimethylbenzene (C36)

Isolated as a clear oil (6.32 g, 89%): ¹H NMR (300 MHz, DMSO-d₆) δ 7.39(s, 2H), 6.17-6.09 (m, 1H), 2.35 (s, 6H); IR (thin film) 1114, 754 cm⁻¹;ESIMS m/z 302 ([M+H]⁺).

2-Bromo-5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichlorobenzene (C37)

Isolated as a clear oil (19 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.54-7.51(m, 2H), 5.03-4.98 (m, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ−70.38.

4-(1-Bromo-2,2-difluoropropyl)-4,2-dichlorobenzene (C38)

Isolated as a colorless liquid (1.40 g, 65%): ¹H NMR (300 MHz, DMSO-d₆)δ 7.76-7.70 (m, 2H), 7.54 (dd, J=8.4, 1.8 Hz, 1H), 5.81-5.73 (m, 1H),1.67 (d, J=18.9 Hz, 3H); IR (thin film) 1118, 800, 499 cm⁻¹; EIMS m/z304 ([M]⁺).

2-Bromo-4-(1-bromo-2,2,2-trifluoroethyl)-1-chlorobenzene (C39)

Isolated as a colorless liquid (10.5 g, 54%): ¹H NMR (400 MHz, CDCl₃) δ7.76 (d, J=1.2 Hz, 1H), 7.49-7.47 (m, 1H), 7.41-7.39 (m, 1H), 5.07-5.02(m, 1H); IR (thin film) 3437, 2924, 1631, 1114 cm⁻¹; EIMS m/z 350([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-fluorobenzene (C40)

Isolated as a colorless oil (8.0 g, 73%): ¹H NMR (300 MHz, CDCl₃) δ7.59-7.57 (m, 1H), 7.42-7.33 (m, 1H), 7.20-7.14 (m, 1H), 5.10-5.03 (m,1H); IR (thin film) 3429, 2926, 1502, 750 cm⁻¹; ESIMS m/z 292 ([M+H]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-1-chloro-2-fluorobenzene (C41)

Isolated as a yellow oil (1.1 g, 45%): ¹H NMR (400 MHz, CDCl₃) δ 7.44(dd, J=8.3, 7.5 Hz, 1H), 7.34 (dd, J=9.5, 1.9 Hz, 1H), 7.26-7.22 (m,1H), 5.08 (q, J=7.1 Hz, 1H); EIMS m/z 291 ([M]⁺).

Example 9: Preparation of5-(1-bromo-2,2-difluorobutyl)-1,2,3-trichlorobenzene (C42)

Triethylamine (2.46 mL, 17.6 mmol) and methanesulfonyl chloride (1.10mL, 14.1 mmol) were added to a solution of2,2-difluoro-1-(3,4,5-trichlorophenyl)butan-1-ol (C44) (3.40 g, 11.7mmol) in dichloromethane (58.7 mL). The reaction mixture was stirred for1 hour, and then pentane was added. Filtration followed by concentrationof the filtrate under vacuum provided a white solid. The solid wasdissolved in dichloromethane (58.7 mL) to which iron(III) bromide (6.94g, 23.5 mmol) was added. The reaction mixture was stirred overnight. Themixture was poured into water and then extracted with dichloromethane.The organics were washed with brine, dried over sodium sulfate,filtered, and concentrated. Purification by flash column chromatographyusing hexanes as eluent provided the title compound as a white solid(3.52 g, 72%): ¹H NMR (400 MHz, CDCl₃) δ 7.51 (s, 2H), 4.85 (t, J=12.1Hz, 1H), 2.14-1.91 (m, 2H), 1.06 (t, J=7.5 Hz, 3H); ¹³C NMR (101 MHz,CDCl₃) δ 135.55, 134.39, 132.52, 129.48, 120.25 (t, J=249.0 Hz), 49.76(t, J=30.3 Hz), 28.03 (t, J=25.2 Hz), 6.06 (t, J=5.1 Hz); ESIMS m/z 351([M−H]⁻).

Example 10: Preparation of2,2-difluoro-1-(3,4,5-trichlorophenyl)propan-1-ol (C43)

2,2-Difluoro-1-(3,4,5-trichlorophenyl)propan-1-one (C52) (1.75 g, 6.40mmol) was dissolved in methanol (64.0 mL) at room temperature and sodiumborohydride (0.290 g, 7.68 mmol) was added. The reaction stirred at roomtemperature for 1 hour, until gas evolution ceased. The reaction mixturewas poured into water and extracted with diethyl ether. The organiclayer was washed with brine, dried over sodium sulfate, filtered, andconcentrated. Purification by flash column chromatography using 0-30%acetone/hexanes as eluent provided the title compound as a clear,colorless oil (1.60 g, 91%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (d, J=0.9Hz, 2H), 4.81 (td, J=8.7, 3.8 Hz, 1H), 1.65-1.41 (m, 3H); ¹⁹F NMR (376MHz, CDCl₃) δ−98.54-−101.73 (m); IR (thin film) 3405, 1555, 1389 cm⁻¹.

The following compounds were prepared in like manner to the procedureoutlined in Example 10:

2,2-Difluoro-1-(3,4,5-trichlorophenyl)butan-1-ol (C44)

Isolated as a clear and colorless oil (3.4 g, 48%): ¹H NMR (400 MHz,CDCl₃) δ 7.48 (d, J=0.9 Hz, 2H), 4.87-4.70 (m, 1H), 2.54 (dt, J=4.0, 1.0Hz, 1H), 2.06-1.82 (m, 1H), 1.82-1.63 (m, 1H), 1.02 (t, J=7.5 Hz, 3H);¹³C NMR (101 MHz, CDCl₃) δ 136.85, 134.20, 131.60, 127.54123.19 (t,J=248.0 Hz), 73.71 (t, J=30.0 Hz), 25.05 (t, J=24.6 Hz), 5.35 (t, J=5.2Hz); EIMS m/z 287 ([M]⁺).

1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-ol (C45)

Isolated as a clear and colorless oil (2.78 g, 89%): ¹H NMR (400 MHz,CDCl₃) δ 7.57 (dd, J=2.0, 0.9 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 7.33-7.27(m, 1H), 4.83 (td, J=8.9, 3.7 Hz, 1H), 2.55 (dt, J=3.8, 1.1 Hz, 1H),1.50 (t, J=18.9 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−99.52 (d, J=249.6Hz), −101.09 (d, J=249.4 Hz); IR (thin film) 3417 cm⁻¹.

Example 11: Preparation of1-(3-bromo-4-chlorophenyl)-2,2,2-trifluoroethanol (C46)

Trimethyl(trifluoromethyl)silane (10.1 mL, 68.4 mmol) andtetrabutylammonium fluoride (1.44 g, 4.56 mmol) were added to a stirredsolution of 3-bromo-4-chloro-benzaldehyde (10.0 g, 45.6 mmol) intetrahydrofuran (150 mL) at room temperature and the reaction mixturewas stirred for 2 hours. The reaction mixture was diluted withdichloromethane and washed with hydrochloric acid (2 N). The separatedorganic layer was washed with brine, dried over sodium sulfate,filtered, and concentrated to afford the title compound as a brownliquid that was used without further purification (13.2 g, 94%):

¹H NMR (300 MHz, CDCl₃) δ 7.76 (s, 1H), 7.50-7.48 (m, 1H), 7.38-7.35 (m,1H), 5.03-4.97 (m, 1H), 2.95 (br s, 1H); IR (thin film) 3406, 2881,1469, 814 cm⁻¹; EIMS m/z 288 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 11:

1-(3,5-Dibromo-4-chlorophenyl)-2,2,2-trifluoroethanol (C47)

Isolated as a pale yellow liquid (7.4 g, 85%): ¹H NMR (400 MHz, DMSO-d₆)δ 7.90 (s, 2H), 7.24 (d, J=5.2 Hz, 1H), 5.33 (d, J=6.4 Hz, 1H); IR (thinfilm) 3370, 1175, 735, 541 cm⁻¹; EIMS m/z 366 ([M]⁺).

1-(4-Chloro-3,5-dimethylphenyl)-2,2,2-trifluoroethanol (C48)

Isolated as a clear liquid (5.0 g, 70%): ¹H NMR (400 MHz, CDCl₃) δ 7.18(s, 2H), 4.95-4.92 (m, 1H), 2.40 (s, 6H); IR (thin film) 3378, 1124, 833cm⁻¹; EIMS m/z 238 ([M]⁺).

1-(4-Bromo-3,5-dichlorophenyl)-2,2,2-trifluoroethanol (C49)

Isolated as a clear oil (33 g, 86%): ¹H NMR (400 MHz, CDCl₃) δ 7.51 (s,2H), 5.01-4.96 (m, 1H), 4.14-4.09 (m, 1H); ¹⁹F NMR (376 MHz, CDCl₃)δ−78.32.

1-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoroethanol (C50)

Isolated as a clear and brown gum (7.0 g, 97%): ¹H NMR (300 MHz, CDCl₃)δ 7.58-7.55 (m, 1H), 7.38-7.33 (m, 1H), 7.20-7.15 (m, 1H), 5.03-4.97 (m,1H); EIMS m/z 228 ([M]⁺).

1-(4-Chloro-3-fluorophenyl)-2,2,2-trifluoroethanol (C51)

Isolated as a clear and colorless oil (1.97 g, 75%); ¹H NMR (400 MHz,CDCl₃) δ 7.52-7.37 (m, 1H), 7.32 (d, J=9.6 Hz, 1H), 7.21 (d, J=8.3 Hz,1H), 5.03 (dd, J=6.3, 3.6 Hz, 1H), 2.62 (d, J=4.0 Hz, 1H); ¹³C NMR (101MHz, CDCl₃) δ 158.06 (d, J_(CF)=250.4 Hz), 134.40 (d, J_(CF) 6.6 Hz),130.79, 123.83 (d, J_(CF)=3.5 Hz), 122.4 (q, J_(CF)=188.9 Hz), 115.8 (d,J=25.3 Hz), 71.65 (q, J_(CF)=31.6 Hz); EIMS m/z 228 ([M]⁺).

Example 12: Preparation of2,2-difluoro-1-(3,4,5-trichlorophenyl)propan-1-one (C52)

To 5-bromo-1,2,3-trichlorobenzene (2.28 g, 8.76 mmol) dissolved indiethyl ether (39.8 mL) at −78° C. under nitrogen was addedn-butyllithium (3.50 mL, 8.76 mmol). The solution was stirred for 30minutes. To this was added ethyl 2,2-difluoropropanoate (1.10 g, 7.96mmol, as a 20% w/w solution in toluene) dropwise over 10 minutes, andthe reaction mixture was stirred for an additional hour. Saturatedaqueous ammonium chloride solution was added to the mixture and stirringwas continued as the reaction flask warmed to room temperature. Thereaction mixture was then extracted with diethyl ether, washed withwater and brine, dried over sodium sulfate, filtered, and concentrated.Purification by flash column chromatography provided the title compoundas a pale yellow oil (1.76 g, 73%): ¹H NMR (400 MHz, CDCl₃) δ 8.11 (d,J=0.9 Hz, 2H), 1.89 (t, J=19.6 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−92.66; ESIMS m/z 271 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 12:

2,2-Difluoro-1-(3,4,5-trichlorophenyl)butan-1-one (C53)

Isolated as an oil (2.3 g, 68%) and used without further purification orcharacterization.

1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-one (C54)

Isolated as a colorless oil (3.89 g, 71%): ¹H NMR (400 MHz, CDCl₃) δ8.21-8.18 (m, 1H), 7.99-7.93 (m, 1H), 7.59 (dd, =8.4, 4.2 Hz, 1H), 1.89(t, J=19.6 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−92.08-−93.21 (m); EIMSm/z 238/240 ([M]⁺).

Example 13: Preparation of4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F16)

Diisopropylethylamine (0.20 mL, 1.1 mmol),benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (0.22g, 0.41 mmol), and (S)—N-(1-aminoethyl)-4,4,4-trifluorobutanamidehydrochloride (C55) (0.086 g, 0.41 mmol) were added to a solution of(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2) (0.18 g, 0.37 mmol) in dichloromethane. The reaction wasstirred for 6 hours at room temperature. The reaction mixture wasdiluted with dichloromethane and washed with water. The organic layerwas dried over sodium sulfate, filtered, and concentrated. Purificationby flash column chromatography using 30% ethyl acetate/petroleum etheras eluent provided the title compound as a pale yellow solid (0.17 g,62%).

Example 14: Preparation of4-((Z)-3-(3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F11)

Diisopropylethylamine (0.19 mL, 1.1 mmol), 1-hydroxy-7-azabenzotriazole(0.059 g, 0.43 mmol), and 2-chloro-1,3-dimethylimidazolidiniumhexafluorophosphate (0.12 g, 0.43 mmol) were added to a solution of(Z)-4-(3-(3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C6) (0.20 g, 0.43 mmol) and(S)—N-(1-aminoethyl)-3,3,3-trifluoropropanamide hydrochloride (C56)(0.099 g, 0.48 mmol) in dichloromethane (5 mL). The reaction mixture wasstirred at room temperature for 6 hours. The reaction mixture wasdiluted with dichloromethane and washed sequentially with hydrochloricacid (2 N) and aqueous sodium bicarbonate. The organic layer wasseparated, washed with water, dried over sodium sulfate, filtered, andconcentrated. Purification by flash column chromatography provided thetitle compound as a white solid (0.11 g, 40%).

The following compounds were prepared in like manner to the procedureoutlined in Example 14:

4-((Z)-3-(3,5-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F12)

Isolated as a yellow gum (0.190 g, 61%).

4-((Z)-3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F13)

Isolated as a yellow gum (0.170 g, 59%).

4-((Z)-3-(3,4-Dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F14)

Isolated as a yellow gum (0.140 g, 48%).

4-((Z)-3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F15)

Isolated as a yellow gum (0.115 g, 45%).

4-((Z)-3-(3,5-Dichloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F17)

Isolated as a yellow solid (0.125 g, 44%).

4-((Z)-3-(3,5-Dichloro-4-vinylphenyl)-1,4,4,4-tetrafluorobut-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F18)

Isolated as an off-white solid (0.130 g, 49%).

4-((Z)-3-(3,5-Dichloro-4-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F19)

Isolated as an off-white solid (0.073 g, 27%).

4-((Z)-3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F22)

Isolated as a pale yellow solid (0.156 g, 61%).

4-((Z)-3-(3,5-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F23)

Isolated as a yellow solid (0.155 g, 56%).

4-((Z)-3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F24)

Isolated as an off-white solid (0.170 g, 55%).

4-((Z)-3-(4-Chloro-3,5-dimethylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F25)

Isolated as a yellow gum (0.170 g, 50%).

4-((Z)-3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F26)

Isolated as a brown solid (0.120 g, 31%).

4-((Z)-3-(3,5-Dibromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F30)

Isolated as a brow gum (0.100 g, 27%).

4-((Z)-3-(4-Bromo-3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F31)

Isolated as a yellow gum (0.109 g, 51%).

4-((Z)-3-(3,4-Dibromophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F32)

Isolated as a yellow solid (0.155 g, 58%).

4-((Z)-3-(3-Bromo-5-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F36)

Isolated as a yellow solid (0.094 g, 42%).

4-((Z)-3-(3-Bromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F37)

Isolated as a yellow gum (0.105 g, 49%).

Example 15: Preparation of4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F1)

To a 25 mL vial was added(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoylchloride (C23) (0.073 g, 0.14 mmol),(S)—N-(1-aminoethyl)-4,4,4-trifluorobutanamide hydrochloride (C55)(0.063 g, 0.28 mmol), and 1,2-dichloroethane (0.71 mL).4-Methylmorpholine (0.070 mL, 0.64 mmol) was added, and the reaction wasallowed to stir for two hours at room temperature. Direct purificationof the reaction mixture by flash column chromatography provided thetitle compound as a colorless oil (0.046 g, 47%).

The following compounds were prepared in like manner to the procedureoutlined in Example 15:

2-Methyl-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(F2)

Isolated as an off-white gum (0.026 g, 25%).

2-Bromo-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(F3)

Isolated as an off-white gum (0.050 g, 37%).

2-Bromo-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F4)

Isolated as a yellow gum (0.047 g, 35%).

4-((Z)-1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F5)

Isolated as an off-white solid (0.061 g, 58%).

2-Methyl-4-((Z)-1,4,4-trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F6)

Isolated as an orange gum (0.028 g, 52%).

2-Chloro-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F7)

Isolated as a yellow gum (0.078 g, 51%).

4-((Z)-1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F8)

Isolated as a white gum (0.062 g, 63%).

2-Chloro-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide

Isolated as a white solid (0.056 g, 37%).

4-((Z)-1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F10)

Isolated as a white foam (0.049 g, 61%).

4-((Z)-1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)hex-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F20)

Isolated as a white foam (0.044 g, 56%).

4-((Z)-1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)hex-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F21)

Isolated as a white foam (0.051 g, 64%).

2-Methyl-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F33)

Isolated as a yellow gum (0.053 g, 36%).

4-((Z)-1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(FC1)

Isolated as a white foam (0.030 g, 37%).

4-((Z)-1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(FC2)

Isolated as a white foam (0.035 g, 42%).

Example 16: Preparation ofN—((R)-1-(cyclopropanecarboxamido)ethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F27)

To a 5 mL vial were added cyclopropanecarboxylic acid (0.0337 g, 0.392mmol) and 1,2-dichloroethane (1.3 mL). Oxalyl dichloride (0.0350 mL,0.409 mmol) and N,N-dimethylformamide (0.986 mg, 0.0130 mmol) wereadded, and the reaction was stirred at room temperature for 3 hours.N—((R)-1-aminoethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamidehydrochloride (C59) (0.150 g, 0.261 mmol) and 4-methylmorpholine (0.0890mL, 0.809 mmol) were added, and the reaction was capped, vortexed, andleft to stir. Direct purification by flash column chromatography using0-100% ethyl acetate/hexanes as eluent followed by purification byreverse phase high pressure liquid chromatography provided the titlecompound as a colorless glass (0.088 g, 50%).

Example 17: Preparation ofN—((R)-1-propionamidoethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F34)

To a 5 mL vial were addedN—((R)-1-aminoethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamidehydrochloride (C59) (0.125 g, 0.218 mmol) and 1,2-dichloroethane (1.3mL). Propionyl chloride (0.0302 mL, 0.327 mmol) and 4-methylmorpholine(0.0718 mL, 0.653 mmol) were added and the reaction was capped,vortexed, and left to stir. Direct purification by flash columnchromatography using 0-100% ethyl acetate/hexanes as eluent provided thetitle compound as a white wax (0.038 g, 27%).

The following compounds were prepared in like manner to the procedureoutlined in Example 17:

4-((Z)-1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)propyl)benzamide(F35)

Isolated as a white solid (0.045 g, 12%).

Example 18: Preparation of4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((S)-1-(2,2,2-trifluoroethylsulfonamido)ethyl)-2-(trifluoromethyl)benzamide(F28)

To a 25 mL vial were addedN—((R)-1-aminoethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamidehydrochloride (C59) (0.150 g, 0.261 mmol), 2,2,2-trifluoroethanesulfonylchloride (0.0572 g, 0.314 mmol), and dioxane (3 mL). 4-Methylmorpholine(0.0720 mL, 0.653 mmol) was added, and the reaction was vertexed severaltimes over a five minute period. A magnetic stir bar was introduced intothe vial, and the reaction was left to stir for 48 hours. Directpurification by flash column chromatography using 0-100% ethylacetate/hexanes as eluent followed by purification by reverse phase highpressure liquid chromatography provided the title compound as acolorless glass (0.0280 g, 15%).

Example 19: Preparation ofN—((S)-1-(3-cyclopropylureido)ethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F29)

N—((R)-1-Aminoethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamidehydrochloride (C59) (0.100 g, 0.174 mmol), isocyanatocyclopropane (0.200g, 2.41 mmol), 2,6-dimethylpyridine (0.0500 mL, 0.429 mmol), andpyridine (0.400 mL) were capped in a 2 mL vial and heated at 80° C. for6 minutes in a Biotage Initiator® microwave reactor with externalIR-sensor temperature monitoring from the side of the vessel. Directpurification by flash column chromatography using 0-100% ethylacetate/hexanes as eluent followed by purification by reverse phase highpressure liquid chromatography provided the title compound as acolorless glass (0.040 g, 35%).

Example 20: Preparation of(S)—N-(1-aminoethyl)-4,4,4-trifluorobutanamide hydrochloride (C55)

(S)—N-(1-Amino-1-oxopropan-2-yl)-4,4,4-trifluorobutanamide (C57) (3.00g, 14.1 mmol) was dissolved in a mixture of water and acetonitrile (1:1,42 mL). [Bis(trifluoroacetoxy)iodo]benzene (6.08 g, 14.1 mmol) wasadded, and the reaction mixture was stirred in a flask wrapped inaluminum foil overnight. The reaction mixture was poured intohydrochloric acid (1 N, 35 mL) and diethyl ether (35 mL). The organiclayer was separated, and the aqueous layer was azeotroped withisopropanol (2×125 mL). Purification by reverse phase flash columnchromatography using 0-100% acetonitrile/water as eluent provided thetitle compound as a white solid (1.50 g, 48%): ¹H NMR (400 MHz, DMSO-d₆)δ 9.11 (d, J=7.4 Hz, 1H), 8.36 (s, 3H), 4.94 (p, J=6.6 Hz, 1H),2.66-2.32 (m, 4H), 1.40 (d, J=6.5 Hz, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆)δ−65.19; ESIMS m/z 185 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 20:

(S)—N-(1-Aminoethyl)-3,3,3-trifluoropropanamide hydrochloride (C56)

Isolated as a white solid (0.300 g, 29%): ¹H NMR (400 MHz, DMSO-d₆) δ9.40 (dd, J=12.1, 6.8 Hz, 1H), 8.38 (s, 3H), 4.97 (p, J=6.6 Hz, 1H),3.52-3.39 (m, 2H), 1.41 (d, J=6.4 Hz, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆)δ−61.32; ESIMS m/z 171 ([M+H]⁺).

Example 21: Preparation of(S)—N-(1-amino-1-oxopropan-2-yl)-4,4,4-trifluorobutanamide (C57)

L-Alaninamide.2H₂O (17.7 g, 97.0 mmol) was dissolved in dioxane (162 mL)to which 4,4,4-trifluorobutanoyl chloride (2.86 mL, 24.2 mmol) wasadded. The reaction mixture was stirred at room temperature for 1 hour,concentrated under reduced pressure, and the solids were dissolved inwater and ethyl acetate. The layers were separated and the aqueous layerwas extracted with ethyl acetate. The combined organic layers werewashed with brine, dried, filtered, and concentrated to provide thedesired compound as a white solid (3.00 g, 58%): ¹H NMR (400 MHz, CDCl₃)δ 8.15 (d, J=7.6 Hz, 1H), 7.32 (s, 1H), 6.97 (s, 1H), 4.20 (p, J=7.2 Hz,1H), 2.53-2.37 (m, 7H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ−65.18; ESIMS m/z213 ([M+H]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 21:

(S)—N-(1-Amino-1-oxopropan-2-yl)-3,3,3-trifluoropropanamide (C58)

Isolated as a white solid (0.9 g, 60%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.38(d, J=7.6 Hz, 1H), 7.43 (s, 1H), 7.04 (s, 1H), 4.25 (p, J=7.2 Hz, 1H),3.32 (q, J=11.4 Hz, 2H), 1.20 (d, J=7.0 Hz, 3H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ−61.44; IR (thin film) 3396, 3304, 3206, 2979, 1711, 1670,1645, 1622, 1546 cm⁻¹.

Example 22: Preparation ofN—((R)-1-aminoethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamidehydrochloride (C59)

To a 25 mL vial were addedN—((R)-1-amino-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C62) (1.13 g, 2.00 mmol), acetonitrile (6.7 mL), water (3.3 mL), andbis(trifluoroacetoxy)iodobenzene (0.687 g, 1.60 mmol) and the reactionmixture was stirred protected from light for 80 minutes. Hydrochloricacid (concentrated, 1 mL) was added, and the reaction was concentratedunder a stream of nitrogen gas. Purification by reverse phasechromatography using 10-100% acetonitrile/water as eluent provided thetitle compound as a pale yellow amorphous solid (0.478 g, 42%): mixtureof diastereomers ¹H NMR (400 MHz, DMSO-d₆) δ 9.61 (d, J=7.4 Hz, 1H),8.56 (s, 3H), 8.18 (d, J=1.7 Hz, 1H), 8.13 (dd, J=8.0, 1.6 Hz, 1H), 8.06(s, 2H), 7.75 (d, J=8.1 Hz, 1H), 6.84 (dd, J=35.7, 10.1 Hz, 1H), 5.27(p, J=9.4 Hz, 1H), 5.15 (t, J=7.5 Hz, 1H), 1.47 (d, J=6.4 Hz, 3H); ¹⁹FNMR (376 MHz, DMSO-d₆) δ−57.88, −57.88, −68.57, −68.58, −113.68,−113.71; ESIMS m/z 535 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 22:

N—((R)-1-Aminopropyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamidehydrochloride (C60)

Isolated as a pale yellow solid (0.210 g, 24%): mixture of diastereomers¹H NMR (400 MHz, DMSO-d₆) δ 9.65-9.44 (m, 1H), 8.44 (s, 3H), 8.25-8.18(m, 1H), 8.19-8.11 (m, 1H), 8.07 (s, 2H), 7.70 (d, J=8.1 Hz, 1H), 6.85(dd, J=35.7, 10.1 Hz, 1H), 5.28 (p, J=9.4 Hz, 1H), 5.01 (dq, J=9.0, 5.2Hz, 1H), 1.97-1.68 (m, 2H), 0.96 (t, J=7.3 Hz, 3H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ−57.95, −68.59, −113.64, −113.67; ESIMS m/z 551 ([M−H]⁻).

Example 23: Preparation ofN—((R)-1-amino-1-oxobutan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C61)

To a 25 mL vial were added(Z)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C2) (1.0 g, 2.0 mmol), oxalyl chloride (0.26 g, 2.0 mmol), anddichloromethane (13 mL). To this solution was addedN,N-dimethylformamide (0.015 mL) and the reaction was stirred while gasevolved. After 2 hours, (R)-ethyl glycinal sodium chloride (0.32 g, 2.0mmol; Prepared by the addition of sodium hydroxide (1 equivalent) to(R)-ethylglycinamide hydrochloride and concentrated.) was added and thereaction mixture was stirred overnight. The reaction mixture was dilutedwith ethyl acetate (200 mL) and washed with hydrochloric acid (0.2 M,3×200 mL). The organic solution was dried over magnesium sulfate,filtered, and concentrated to provide the title compound as an orangefoam (0.82 g, 60%): ¹H NMR (500 MHz, CDCl₃) δ 7.82 (d, J=1.8 Hz, 1H),7.76-7.67 (m, 1H), 7.53 (d, J=8.1 Hz, 1H), 7.44 (s, 2H), 7.13-7.03 (m,1H), 6.84 (s, 1H), 6.06 (s, 1H), 5.83 (dd, J=32.6, 9.6 Hz, 1H), 4.72(dt, J=7.8, 6.6 Hz, 1H), 4.60 (p, J=8.9 Hz, 1H), 1.93 (ddd, J=13.8, 7.6,6.2 Hz, 1H), 1.77 (dp, J=14.4, 7.3 Hz, 1H), 0.98 (t, J=7.4 Hz, 3H); ¹⁹FNMR (471 MHz, CDCl₃) δ−59.29, −69.36 (t, J=7.3 Hz), −112.12 (dd, J=32.7,8.2 Hz); ESIMS m/z 579 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 23:

N—((R)-1-Amino-1-oxopropan-2-yl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C62)

Isolated as an orange foam (1.13 g, 89%): ¹H NMR (400 MHz, CDCl₃) δ7.86-7.82 (m, 1H), 7.74 (dd, J=8.1, 1.7 Hz, 1H), 7.56 (d, J=8.1 Hz, 1H),7.44 (s, 2H), 6.94 (dd, J=7.5, 2.9 Hz, 1H), 6.64 (s, 1H), 5.91-5.74 (m,2H), 4.79 (p, J=7.1 Hz, 1H), 4.61 (p, J=8.9 Hz, 1H), 1.50 (d, J=7.0 Hz,3H); ¹⁹F NMR (376 MHz, CDCl₃) δ−59.18, −69.34 (m), −112.05; ESIMS m/z565 ([M−H]⁻).

The following molecules in Table 0.1 may be prepared according to theprocedures disclosed: P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12,P13, P14, P15, P16, P17, P18, P19, P20, P21, P22, P23, P24, P25, P26,P27, P28, P29, P30, and P31.

TABLE 1 Structure and Preparation Method for Prophetic Molecules No.Structure P1

P2

P3

P4

P5

P6

P7

P8

P9

P10

P11

P12

P13

P14

P15

P16

P17

P18

P19

P20

P21

P22

P23

P24

P25

P26

P27

P28

P29

P30

P31

The following compounds were prepared in like manner to the procedureoutlined in Example 1:

(Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-1-naphthoicacid (C63)

Isolated as a yellow solid (0.85 g, 5): ¹H NMR (300 MHz, CDCl₃) δ 8.30(d, J=7.5 Hz, 1H), 8.07-8.05 (m, 1H), 7.70-7.61 (m, 4H), 7.49 (s, 2H),5.69 (dd, 1=9.9, 31.2 Hz, 1H), 4.75-4.69 (m, 1H); IR (thin film) 3445,1684, 1260, 750 cm⁻¹; ESIMS m/z 475.23 ([M]⁻).

(Z)-4-(3-(3,4-Dichloro-5-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C64)

Isolated as a brown gum (1.7 g, 42%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.80(s, 1H), 8.14 (s, 1H), 8.09 (d, J=8.1 Hz, 1H), 7.91 (d, J=8.1 Hz, 1H),7.83 (s, 1H), 7.65 (s, 1H), 6.87 (dd, J=9.9, 36.0 Hz, 1H), 5.13-5.07 (m,1H), 2.42 (s, 3H); IR (thin film) 3446, 2928, 1716 cm⁻¹; ESIMS m/z473.10 ([M−H]⁻).

(Z)-4-(3-(4-Bromo-3-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C65)

Isolated as a brown gum (2.5 g, 68%): ¹H NMR ((400 MHz, CDCl₃) δ 8.02(d, J=8.4 Hz, 1H), 7.94 (s, 1H), 7.83 (d, J=7.2 Hz, 1H), 7.66 (d, =8.4Hz, 1H), 7.50 (s, 1H), 7.17 (dd, =8.4 Hz, 1H), 5.96 (dd, J=9.2, 32.0 Hz,1H), 4.65-4.61 (m, 1H); IR (thin film) 3447, 2927, 1715, 750 cm⁻¹; ESIMSm/z 504.4 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 7:

(4-(1-Fluorovinyl)-1-naphthoic acid (C66)

Isolated as an off-white solid (0.70 g, 52%): mp 154-156° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 13.40 (br s, 1H), 8.88-8.84 (m, 1H), 8.17-8.10 (m,2H), 7.75-7.66 (m, 3H), 5.39 (dd, J=3.6, 17.2 Hz, 1H), 5.23 (dd, J=36.0,50.4 Hz, 1H); ESIMS m/z 215.20 ([M−H]⁻).

The following compounds were prepared in like manner to the procedureoutlined in Example 8:

1-Bromo-4-(1-bromo-2,2,2-trifluoroethyl)-2-chlorobenzene (C67)

Isolated as a colorless oil (TO g, 51%); ¹H NMR (400 MHz, CDCl₃) δ7.75-7.72 (m, 1H), 7.65-7.61 (m, 1H), 7.26-7.21 (m, 1H), 5.08-5.02 (m,1H); ESIMS m/z 350.0 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichloro-3-methylbenzene (C70)

Isolated as a clear oil (6.7 g, 67%): ¹H NMR (300 MHz, CDCl₃) δ 7.46 (s,1H), 7.28 (s, 1H), 5.02 (q, J=7.2 Hz, 1H), 2.45 (s, 3H); IR (thin film)1260, 1113, 750 cm⁻¹; EIMS m/z 322 ([M]⁺).

The following compound was prepared in like manner to the procedureoutlined in Example 10:

1-(3,4-Dichloro-5-methylphenyl)-2,2,2-trifluoroethan-1-ol (C71)

Isolated as a pale yellow oil (4.6 g, 79%): ¹H NMR (300 MHz, CDCl₃) δ7.44 (s, 1H), 7.26 (s, 1H), 4.97 (q, J=6.6 Hz, 1H), 2.44 (s, 3H); IR(thin film) 3428, 1275, 1262, 750 cm⁻¹; EIMS m/z 258 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 11:

1-(4-Bromo-3-chlorophenyl)-2,2,2-trifluoroethan-1-ol (C68)

Isolated as a brown gum (12 g, 77%): ¹H NMR (400 MHz, CDCl₃) δ 7.65-7.60(m, 1H), 7.59 (s, 1H), 7.23-7.19 (m, 1H), 5.09-5.01 (m, 1H), 2.86 (br s,1H); ESIMS m/z 289.90 ([M]⁺).

The following compounds were prepared in like manner to the procedureoutlined in Example 14:

4-((Z)-1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)-1-naphthamide(PF1)

Isolated as a yellow solid (0.128 g, 64%).

4-((Z)-3-(4-Chloro-3-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(PF2)

Isolated as a yellow solid (0.120 g, 50%).

4-((Z)-3-(3-Chloro-4-fluorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(PF3)

Isolated as a yellow gum (0.090 g, 36%).

4-((Z)-3-(3,4-Dichloro-5-methylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(PF4)

Isolated as a brown gum (0.180 g, 66%).

4-((Z)-3-(4-Bromo-3-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(PF8)

Isolated as an off-white solid (0.050 g, 21%).

4-((Z)-3-(3-Bromo-4-chlorophenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(PF13)

Isolated as a yellow gum (0.090 g, 32%).

The following compounds were prepared in like manner to the procedureoutlined in Example 16:

4-((Z)-3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F39)

Isolated as a white foam (0.099 g, 83%).

4-((Z)-3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F40)

Isolated as a white foam (0.077 g, 62.8%).

N—((R)-1-(3-Cyanopropanamido)ethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F41)

Isolated as a colorless glass (0.049 g, 29%).

N—((S)-1-(1-Cyanocyclopropane-1-carboxamido)ethyl)-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(PF31)

Isolated as a colorless foam (0.15 g, 82%).

Example 24 Preparation of 4-vinyl-1-naphthoic acid (C69)

To a stirred solution of 4-bromo-1-naphthoic acid (2.50 g, 9.98 mmol) indimethyl sulfoxide (32.3 mL) was added potassium vinyltrifluoroborate(1.33 g, 9.96 mmol), potassium carbonate (3.85 g, 27.9 mmol) and[1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.364 g,0.498 mmol). The reaction mixture was heated in an 80° C. bath for 18hours. The reaction mixture was cooled to ambient temperature anddiluted with 1 N aqueous hydrochloric acid solution (150 mL) and water(150 mL). The mixture was extracted with ethyl acetate. The organiclayer was washed with brine, dried over sodium sulfate and concentratedunder reduced pressure to afford the crude compound. The crude compoundwas purified by column chromatography (SiO₂, eluting with 0-100% ethylacetate in hexanes) to afford the title compound as a bright yellowsolid (1.36 g, 62%): mp 147-155° C.; ¹H NMR (300 MHz, acetone-d₆) δ11.42 (s, 1H), 9.16-9.03 (m, 1H), 8.31-8.25 (m, 2H), 7.77 (dd, J=7.7,0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd,J=11.1, 1.5 Hz, 1H); ESIMS m/z 197.1 ([M−H]⁻).

Example 25: Preparation of1-(3,4-dichloro-5-methylphenyl)-2,2,2-trifluoroethan-1-one (C72)

To 5-bromo-1,2-dichloro-3-methylbenzene (6.9 g, 29 mmol) intetrahydrofuran (65 mL) cooled in an ice bath under nitrogen was addedisopropylmagnesium chloride lithium chloride complex in tetrahydrofuran(26.8 mL, 34.8 mmol). After 1 hour methyl 2,2,2-trifluoroacetate (3.79mL, 37.7 mmol) was added. After 30 minutes, the ice bath was removed,and the solution was stirred for 1 hour. The reaction mixture wasquenched with aqueous hydrochloric acid (2 N). The mixture wasconcentrated and extracted with dichloromethane. The organic layer waswashed with brine, dried over sodium sulfate, filtered, andconcentrated. Purification by column chromatography (SiO₂, petroleumether) provided the title compound as a white solid (5.9 g, 80%); ¹H NMR(400 MHz, CDCl₃) δ 8.00 (s, 1H), δ 7.83 (s, 1H), 2.51 (s, 3H); EIMS m/z256 ([M]⁺).

Biological Assays

The following bioassays against Beet Armyworm (Spodoptera exigua),Cabbage Looper (Trichoplusia ni), Corn Earworm (Helicoverpa zea), GreenPeach Aphid (Myzus persicae), and Yellow Fever Mosquito (Aedes aegypti),are included herein due to the damage they inflict. Furthermore, theBeet Armyworm, Corn Earworm, and Cabbage Looper are three good indicatorspecies for a broad range of chewing pests. Additionally, the GreenPeach Aphid is a good indicator species for a broad range of sap-feedingpests. The results with these four indicator species along with theYellow Fever Mosquito show the broad usefulness of the molecules ofFormula One in controlling pests in Phyla Arthropoda, Mollusca, andNematoda (For further information see Methods for the Design andOptimization of New Active Ingredients, Modern Methods in CropProtection Research, Edited by Jeschke, P., Kramer, W., Schirmer, U.,and Matthias W., p. 1-20, 2012).

Example A: Bioassays on Beet Armyworm (Spodoptera exigua, LAPHEG)(“BAW”), Corn Earworm (Helicoverpa zea, HELIZE) (“CEW”), and CabbageLooper (Trichoplusia ni, TRIPNI) (“CL”)

Beet army worm is a serious pest of economic concern for alfalfa,asparagus, beets, citrus, corn, cotton, onions, peas, peppers, potatoes,soybeans, sugar beets, sunflowers, tobacco, tomatoes, among other crops.It is native to Southeast Asia but is now found in Africa, Australia,Japan, North America, and Southern Europe. The larvae may feed in largeswarms causing devastating crop losses. It is known to be resistant toseveral pesticides.

Cabbage Looper is a serious pest found throughout the world. It attacksalfalfa, beans, beets, broccoli, Brussel sprouts, cabbage, cantaloupe,cauliflower, celery, collards, cotton, cucumbers, eggplant, kale,lettuce, melons, mustard, parsley, peas, peppers, potatoes, soybeans,spinach, squash, tomatoes, turnips, and watermelons, among other crops.This species is very destructive to plants due to its voraciousappetite. The larvae consume three times their weight in food daily. Thefeeding sites are marked by large accumulations of sticky, wet, fecalmaterial. It is known to be resistant to several pesticides.

Corn earworm is considered by some to be the most costly crop pest inNorth America. It often attacks valuable crops, and the harvestedportion of the crop. This pest damages alfalfa, artichoke, asparagus,cabbage, cantaloupe, collard, corn, cotton, cowpea, cucumber, eggplant,lettuce, lima bean, melon, okra, pea, pepper, potato, pumpkin, snapbean, soybean, spinach, squash, sugarcane, sweet potato, tomato, andwatermelon, among other crops. Furthermore, this pest is also known tobe resistant to certain insecticides.

Consequently, because of the above factors control of these pests isimportant. Furthermore, molecules that control these pests (BAW, CEW,and CL), which are known as chewing pests, are useful in controllingother pests that chew on plants.

Certain molecules disclosed in this document were tested against BAW,CEW, and CL using procedures described in the following examples. In thereporting of the results, the “BAW, CEW, & CL Rating Table” was used(See Table Section).

Bioassays on BAW

Bioassays on BAW were conducted using a 128-well diet tray assay. one tofive second instar BAW larvae were placed in each well (3 mL) of thediet tray that had been previously filled with 1 mL of artificial dietto which 50 μg/cm² of the test molecule (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesive coverand held at 25° C., 14:10 light-dark for five to seven days. Percentmortality was recorded for the larvae in each well; activity in theeight wells was then averaged. The results are indicated in the tableentitled “Table ABC: Biological Results” (See Table Section).

Bioassays on CL

Bioassays on CL were conducted using a 128-well diet tray assay. one tofive second instar CL larvae were placed in each well (3 mL) of the diettray that had been previously filled with 1 mL of artificial diet towhich 50 μg/cm² of the test molecule (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesive coverand held at 25° C., 14:10 light-dark for five to seven days. Percentmortality was recorded for the larvae in each well; activity in theeight wells was then averaged. The results are indicated in the tableentitled “Table ABC: Biological Results” (See Table Section).

Example B: Bioassays on Green Peach Aphid (Myzus persicae, MYZUPE)(“GPA”)

GPA is the most significant aphid pest of peach trees, causing decreasedgrowth, shriveling of the leaves, and the death of various tissues. Itis also hazardous because it acts as a vector for the transport of plantviruses, such as potato virus Y and potato leafroll virus to members ofthe nightshade/potato family Solanaceae, and various mosaic viruses tomany other food crops. GPA attacks such plants as broccoli, burdock,cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce,macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, andzucchini, among other crops. GPA also attacks many ornamental crops suchas carnation, chrysanthemum, flowering white cabbage, poinsettia, androses. GPA has developed resistance to many pesticides. Consequently,because of the above factors control of this pest is important.Furthermore, molecules that control this pest (GPA), which is known as asap-feeding pest, are useful in controlling other pests that feed on thesap from plants.

Certain molecules disclosed in this document were tested against GPAusing procedures described in the following example. In the reporting ofthe results, the “GPA & YFM Rating Table” was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 GPA (wingless adult and nymph stages) one day prior to chemicalapplication. Four pots with individual seedlings were used for eachtreatment. Test molecules (2 mg) were dissolved in 2 mL ofacetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm testmolecule. The stock solutions were diluted 5× with 0.025% Tween 20 inwater to obtain the solution at 200 ppm test molecule. A hand-heldaspirator-type sprayer was used for spraying a solution to both sides ofcabbage leaves until runoff. Reference plants (solvent check) weresprayed with the diluent only containing 20% by volume ofacetone/methanol (1:1) solvent. Treated plants were held in a holdingroom for three days at approximately 25° C. and ambient relativehumidity (RH) prior to grading. Evaluation was conducted by counting thenumber of live aphids per plant under a microscope. Percent Control wasmeasured by using Abbott's correction formula (W. S. Abbott, “A Methodof Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18(1925), pp. 265-267) as follows.

Corrected % Control=100*(X−Y)/X

-   -   where    -   X=No. of live aphids on solvent check plants and    -   Y=No. of live aphids on treated plants

The results are indicated in the table entitled “Table ABC: BiologicalResults” (See Table Section).

Example C: Bioassays on Yellow Fever Mosquito (Aedes aegypti, AEDSAE)(“YFM”)

YFM prefers to feed on humans during the daytime and is most frequentlyfound in or near human habitations. YFM is a vector for transmittingseveral diseases. It is a mosquito that can spread the dengue fever andyellow fever viruses. Yellow fever is the second most dangerousmosquito-borne disease after malaria. Yellow fever is an acute viralhemorrhagic disease and up to 50% of severely affected persons withouttreatment will die from yellow fever. There are an estimated 200,000cases of yellow fever, causing 30,000 deaths, worldwide each year.Dengue fever is a nasty, viral disease; it is sometimes called“breakbone fever” or “break-heart fever” because of the intense pain itcan produce. Dengue fever kills about 20,000 people annually.Consequently, because of the above factors control of this pest isimportant. Furthermore, molecules that control this pest (YFM), which isknown as a sucking pest, are useful in controlling other pests thatcause human and animal suffering.

Certain molecules disclosed in this document were tested against YFMusing procedures described in the following paragraph. In the reportingof the results, the “GPA & YFM Rating Table” was used (See TableSection).

Master plates containing 400 μg of a molecule dissolved in 100 μL ofdimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used.A master plate of assembled molecules contains 15 μL per well. To thisplate, 135 μL of a 90:10 water:acetone mixture is added to each well. Arobot (Biomek® NXP Laboratory Automation Workstation) is programmed todispense 15 μL aspirations from the master plate into an empty 96-wellshallow plate (“daughter” plate). There are 6 reps (“daughter” plates)created per master. The created daughter plates are then immediatelyinfested with YFM larvae.

The day before plates are to be treated, mosquito eggs are placed inMillipore water containing liver powder to begin hatching (4 g. into 400mL). After the daughter plates are created using the robot, they areinfested with 220 μL of the liver powder/larval mosquito mixture (about1 day-old larvae). After plates are infested with mosquito larvae, anon-evaporative lid is used to cover the plate to reduce drying. Platesare held at room temperature for 3 days prior to grading. After 3 days,each well is observed and scored based on mortality. The results areindicated in the table entitled “Table ABC: Biological Results” (SeeTable Section).

Agriculturally Acceptable Acid Addition Salts, Salt Derivatives,Solvates, Ester Derivatives, Polymorphs, Isotopes, and Radionuclides

Molecules of Formula One may be formulated into agriculturallyacceptable acid addition salts. By way of a non-limiting example, anamine function can form salts with hydrochloric, hydrobromic, sulfuric,phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric,oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic,aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic,hydroxyl-methanesulfonic, and hydroxyethanesulfonic acids. Additionally,by way of a non-limiting example, an acid function can form saltsincluding those derived from alkali or alkaline earth metals and thosederived from ammonia and amines. Examples of preferred cations includesodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By wayof a non-limiting example, a salt derivative may be prepared bycontacting a free base with a sufficient amount of the desired acid toproduce a salt. A free base may be regenerated by treating the salt witha suitable dilute aqueous base solution such as dilute aqueous sodiumhydroxide, potassium carbonate, ammonia, and sodium bicarbonate. As anexample, in many cases, a pesticide, such as 2,4-D, is made morewater-soluble by converting it to its dimethylamine salt.

Molecules of Formula One may be formulated into stable complexes with asolvent, such that the complex remains intact after the non-complexedsolvent is removed. These complexes are often referred to as “solvates.”However, it is particularly desirable to form stable hydrates with wateras the solvent.

Molecules of Formula One may be made into ester derivatives. These esterderivatives can then be applied in the same manner as the moleculesdisclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs.Polymorphism is important in the development of agrochemicals sincedifferent crystal polymorphs or structures of the same molecule can havevastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Ofparticular importance are molecules having ²H (also known as deuterium)or ³H (also known as tritium) in place of 1H. Molecules of Formula Onemay be made with different radionuclides. Of particular importance aremolecules having ¹⁴C. Molecules of Formula One having deuterium,tritium, or ¹⁴C may be used in biological studies allowing tracing inchemical and physiological processes and half-life studies, as well as,MoA studies.

Stereoisomers

Molecules of Formula One may exist as one or more stereoisomers. Thus,certain molecules may be produced as racemic mixtures. It will beappreciated by those skilled in the art that one stereoisomer may bemore active than the other stereoisomers. Individual stereoisomers maybe obtained by known selective synthetic procedures, by conventionalsynthetic procedures using resolved starting materials, or byconventional resolution procedures. Certain molecules disclosed in thisdocument can exist as two or more isomers. The various isomers includegeometric isomers, diastereomers, and enantiomers. Thus, the moleculesdisclosed in this document include geometric isomers, racemic mixtures,individual stereoisomers, and optically active mixtures. It will beappreciated by those skilled in the art that one isomer may be moreactive than the others. The structures disclosed in the presentdisclosure are drawn in only one geometric form for clarity, but areintended to represent all geometric forms of the molecule.

Combinations

In another embodiment of this invention, molecules of Formula One may beused in combination (such as, in a compositional mixture, or asimultaneous or sequential application) with one or more activeingredients.

In another embodiment of this invention, molecules of Formula One may beused in combination (such as, in a compositional mixture, or asimultaneous or sequential application) with one or more activeingredients each having a MoA that is the same as, similar to, but morelikely—different from, the MoA of the molecules of Formula One.

In another embodiment, molecules of Formula One may be used incombination (such as, in a compositional mixture, or a simultaneous orsequential application) with one or more molecules having acaricidal,algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal,molluscicidal, nematicidal, rodenticidal, and/or virucidal properties.

In another embodiment, the molecules of Formula One may be used incombination (such as, in a compositional mixture, or a simultaneous orsequential application) with one or more molecules that areantifeedants, bird repellents, chemosterilants, herbicide safeners,insect attractants, insect repellents, mammal repellents, matingdisrupters, plant activators, plant growth regulators, and/orsynergists.

In another embodiment, molecules of Formula One may also be used incombination (such as in a compositional mixture, or a simultaneous orsequential application) with one or more biopesticides.

In another embodiment, in a pesticidal composition combinations of amolecule of Formula One and an active ingredient may be used in a widevariety of weight ratios. For example, in a two component mixture, theweight ratio of a molecule of Formula One to an active ingredient, maybe from about 100:1 to about 1:100; in another example the weight ratiomay be about 50:1 to about 1:50; in another example the weight ratio maybe about 20:1 to about 1:20; in another example the weight ratio may beabout 10:1 to about 1:10; in another example the weight ratio may beabout 5:1 to 1:5; in another example the weight ratio may be about 3:1to about 1:3; in another example the weight ratio may be about 2:1 toabout 1:2; and in a final example the weight ratio may be about 1:1 (SeeTable B). However, in general, weight ratios less than about 10:1 toabout 1:10 are preferred. It is also preferred sometimes to use a threeor four component mixture comprising a molecule of Formula One and oneor more active ingredients.

TABLE B Weight Ratios Molecule of the Formula One:active ingredient100:1 to 1:100 50:1 to 1:50 20:1 to 1:20 10:1 to 1:10 5:1 to 1:5 3:1 to1:3 2:1 to 1:2 1:1

Weight ratios of a molecule of Formula One to an active ingredient mayalso be depicted as X:Y; wherein X is the parts by weight of a moleculeof Formula One and Y is the parts by weight of active ingredient. Thenumerical range of the parts by weight for X is 0<X≦100 and the parts byweight for Y is 0<Y≦100 and is shown graphically in TABLE C. By way ofnon-limiting example, the weight ratio of a molecule of Formula One toan active ingredient may be 20:1.

TABLE C active 100 X, Y X, Y X, Y ingredient 50 X, Y X, Y X, Y X, Y X, Y(Y) 20 X, Y X, Y X, Y X, Y X, Y Parts by 15 X, Y X, Y X, Y X, Y X, Yweight 10 X, Y X, Y 5 X, Y X, Y X, Y X, Y 3 X, Y X, Y X, Y X, Y X, Y X,Y X, Y 2 X, Y X, Y X, Y X, Y X, Y 1 X, Y X, Y X, Y X, Y X, Y X, Y X, YX, Y X, Y 1 2 3 5 10 15 20 50 100 molecule of Formula One (X) Parts byweight

Ranges of weight ratios of a molecule of Formula One to an activeingredient may be depicted as X₁:Y₁ to X₂:Y₂, wherein X and Y aredefined as above.

In one embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁>Y₁ and X₂<Y₂. By way of non-limiting example, the range of aweight ratio of a molecule of Formula One to an active ingredient may bebetween 3:1 and 1:3, inclusive of the endpoints.

In another embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁>Y₁ and X₂>Y₂. By way of non-limiting example, the range ofweight ratio of a molecule of Formula One to an active ingredient may bebetween 15:1 and 3:1, inclusive of the endpoints.

In another embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂, wherein X₁<Y₁ and X₂<Y₂. By way of non-limiting example, the rangeof weight ratios of a molecule of Formula One to an active ingredientmay be between about 1:3 and about 1:20, inclusive of the endpoints.

Formulations

A pesticide is rarely suitable for application in its pure form. It isusually necessary to add other substances so that the pesticide may beused at the required concentration and in an appropriate form,permitting ease of application, handling, transportation, storage, andmaximum pesticide activity. Thus, pesticides are formulated into, forexample, baits, concentrated emulsions, dusts, emulsifiableconcentrates, fumigants, gels, granules, microencapsulations, seedtreatments, suspension concentrates, suspoemulsions, tablets, watersoluble liquids, water dispersible granules or dry flowables, wettablepowders, and ultra-low volume solutions.

Pesticides are applied most often as aqueous suspensions or emulsionsprepared from concentrated formulations of such pesticides. Suchwater-soluble, water-suspendable, or emulsifiable formulations areeither solids, usually known as wettable powders, or water dispersiblegranules, or liquids usually known as emulsifiable concentrates, oraqueous suspensions. Wettable powders, which may be compacted to formwater dispersible granules, comprise an intimate mixture of thepesticide, a carrier, and surfactants. The concentration of thepesticide is usually from about 10% to about 90% by weight. The carrieris usually selected from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among sulfonated lignins,condensed naphthalenesulfonates, naphthalenesulfonates,alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants suchas ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenientconcentration of a pesticide, such as from about 50 to about 500 gramsper liter of liquid dissolved in a carrier that is either a watermiscible solvent or a mixture of water-immiscible organic solvent andemulsifiers. Useful organic solvents include aromatics, especiallyxylenes and petroleum fractions, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as the terpenicsolvents including rosin derivatives, aliphatic ketones such ascyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitableemulsifiers for emulsifiable concentrates are selected from conventionalanionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticidesdispersed in an aqueous carrier at a concentration in the range fromabout 5% to about 50% by weight. Suspensions are prepared by finelygrinding the pesticide and vigorously mixing it into a carrier comprisedof water and surfactants. Ingredients, such as inorganic salts andsynthetic or natural gums may also be added, to increase the density andviscosity of the aqueous carrier. It is often most effective to grindand mix the pesticide at the same time by preparing the aqueous mixtureand homogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

Pesticides may also be applied as granular compositions that areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the pesticide,dispersed in a carrier that comprises clay or a similar substance. Suchcompositions are usually prepared by dissolving the pesticide in asuitable solvent and applying it to a granular carrier which has beenpre-formed to the appropriate particle size, in the range of from about0.5 to about 3 mm. Such compositions may also be formulated by making adough or paste of the carrier and molecule and crushing and drying toobtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing thepesticide in powdered form with a suitable dusty agricultural carrier,such as kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from about 1% to about 10% of the pesticide. Dusts maybe applied as a seed dressing or as a foliage application with a dustblower machine.

It is equally practical to apply a pesticide in the form of a solutionin an appropriate organic solvent, usually petroleum oil, such as thespray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. Insuch compositions the pesticide is dissolved or dispersed in a carrier,which is a pressure-generating propellant mixture. The aerosolcomposition is packaged in a container from which the mixture isdispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or anattractant or both. When the pests eat the bait they also consume thepesticide. Baits may take the form of granules, gels, flowable powders,liquids, or solids. Baits may be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure andhence can exist as a gas in sufficient concentrations to kill pests insoil or enclosed spaces. The toxicity of the fumigant is proportional toits concentration and the exposure time. They are characterized by agood capacity for diffusion and act by penetrating the pest'srespiratory system or being absorbed through the pest's cuticle.Fumigants are applied to control stored product pests under gas proofsheets, in gas sealed rooms or buildings or in special chambers.

Pesticides may be microencapsulated by suspending the pesticideparticles or droplets in plastic polymers of various types. By alteringthe chemistry of the polymer or by changing factors in the processing,microcapsules may be formed of various sizes, solubility, wallthicknesses, and degrees of penetrability. These factors govern thespeed with which the active ingredient within is released, which inturn, affects the residual performance, speed of action, and odor of theproduct.

Oil solution concentrates are made by dissolving pesticide in a solventthat will hold the pesticide in solution. Oil solutions of a pesticideusually provide faster knockdown and kill of pests than otherformulations due to the solvents themselves having pesticidal action andthe dissolution of the waxy covering of the integument increasing thespeed of uptake of the pesticide. Other advantages of oil solutionsinclude better storage stability, better penetration of crevices, andbetter adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsioncomprises oily globules which are each provided with a lamellar liquidcrystal coating and are dispersed in an aqueous phase, wherein each oilyglobule comprises at least one molecule which is agriculturally active,and is individually coated with a monolamellar or oligolamellar layercomprising: (1) at least one non-ionic lipophilic surface-active agent,(2) at least one non-ionic hydrophilic surface-active agent and (3) atleast one ionic surface-active agent, wherein the globules having a meanparticle diameter of less than 800 nanometers.

Other Formulation Components

Generally, when the molecules disclosed in Formula One are used in aformulation, such formulation can also contain other components. Thesecomponents include, but are not limited to, (this is a non-exhaustiveand non-mutually exclusive list) wetters, spreaders, stickers,penetrants, buffers, sequestering agents, drift reduction agents,compatibility agents, anti-foam agents, cleaning agents, andemulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases thespreading or penetration power of the liquid by reducing the interfacialtension between the liquid and the surface on which it is spreading.Wetting agents are used for two main functions in agrochemicalformulations: during processing and manufacture to increase the rate ofwetting of powders in water to make concentrates for soluble liquids orsuspension concentrates; and during mixing of a product with water in aspray tank to reduce the wetting time of wettable powders and to improvethe penetration of water into water-dispersible granules. Examples ofwetting agents used in wettable powder, suspension concentrate, andwater-dispersible granule formulations are: sodium lauryl sulfate;sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphaticalcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface ofparticles and helps to preserve the state of dispersion of the particlesand prevents them from reaggregating. Dispersing agents are added toagrochemical formulations to facilitate dispersion and suspension duringmanufacture, and to ensure the particles redisperse into water in aspray tank. They are widely used in wettable powders, suspensionconcentrates and water-dispersible granules. Surfactants that are usedas dispersing agents have the ability to adsorb strongly onto a particlesurface and provide a charged or steric barrier to reaggregation ofparticles. The most commonly used surfactants are anionic, non-ionic, ormixtures of the two types. For wettable powder formulations, the mostcommon dispersing agents are sodium lignosulfonates. For suspensionconcentrates, very good adsorption and stabilization are obtained usingpolyelectrolytes, such as sodium naphthalene sulfonate formaldehydecondensates. Tristyrylphenol ethoxylate phosphate esters are also used.Non-ionics such as alkylarylethylene oxide condensates and EO-PO blockcopolymers are sometimes combined with anionics as dispersing agents forsuspension concentrates. In recent years, new types of very highmolecular weight polymeric surfactants have been developed as dispersingagents. These have very long hydrophobic ‘backbones’ and a large numberof ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant.These high molecular weight polymers can give very good long-termstability to suspension concentrates because the hydrophobic backboneshave many anchoring points onto the particle surfaces. Examples ofdispersing agents used in agrochemical formulations are: sodiumlignosulfonates; sodium naphthalene sulfonate formaldehyde condensates;tristyrylphenol ethoxylate phosphate esters; aliphatic alcoholethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graftcopolymers.

An emulsifying agent is a substance which stabilizes a suspension ofdroplets of one liquid phase in another liquid phase. Without theemulsifying agent the two liquids would separate into two immiscibleliquid phases. The most commonly used emulsifier blends containalkylphenol or aliphatic alcohol with twelve or more ethylene oxideunits and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. Arange of hydrophile-lipophile balance (“HLB”) values from 8 to 18 willnormally provide good stable emulsions. Emulsion stability can sometimesbe improved by the addition of a small amount of an EO-PO blockcopolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in waterat concentrations above the critical micelle concentration. The micellesare then able to dissolve or solubilize water-insoluble materials insidethe hydrophobic part of the micelle. The types of surfactants usuallyused for solubilization are non-ionics, sorbitan monooleates, sorbitanmonooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additivessuch as mineral or vegetable oils as adjuvants to spray-tank mixes toimprove the biological performance of the pesticide on the target. Thetypes of surfactants used for bioenhancement depend generally on thenature and mode of action of the pesticide. However, they are oftennon-ionics such as: alkyl ethoxylates; linear aliphatic alcoholethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material addedto the pesticide to give a product of the required strength. Carriersare usually materials with high absorptive capacities, while diluentsare usually materials with low absorptive capacities. Carriers anddiluents are used in the formulation of dusts, wettable powders,granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiableconcentrates, oil-in-water emulsions, suspoernulsions, and ultra-lowvolume formulations, and to a lesser extent, granular formulations.Sometimes mixtures of solvents are used. The first main groups ofsolvents are aliphatic paraffinic oils such as kerosene or refinedparaffins. The second main group (and the most common) comprises thearomatic solvents such as xylene and higher molecular weight fractionsof C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful ascosolvents to prevent crystallization of pesticides when the formulationis emulsified into water. Alcohols are sometimes used as cosolvents toincrease solvent power. Other solvents may include vegetable oils, seedoils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation ofsuspension concentrates, emulsions and suspoemulsions to modify therheology or flow properties of the liquid and to prevent separation andsettling of the dispersed particles or droplets. Thickening, gelling,and anti-settling agents generally fall into two categories, namelywater-insoluble particulates and water-soluble polymers. It is possibleto produce suspension concentrate formulations using clays and silicas.Examples of these types of materials, include, but are not limited to,montmorillonite, bentonite, magnesium aluminum silicate, andattapulgite. Water-soluble polysaccharides have been used asthickening-gelling agents for many years. The types of polysaccharidesmost commonly used are natural extracts of seeds and seaweeds or aresynthetic derivatives of cellulose. Examples of these types of materialsinclude, but are not limited to, guar gum; locust bean gum; carrageenam;alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC);hydroxyethyl cellulose (HEC). Other types of anti-settling agents arebased on modified starches, polyacrylates, polyvinyl alcohol andpolyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Thereforepreservation agents are used to eliminate or reduce their effect.Examples of such agents include, but are not limited to: propionic acidand its sodium salt; sorbic acid and its sodium or potassium salts;benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt;methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations tofoam during mixing operations in production and in application through aspray tank. In order to reduce the tendency to foam, anti-foam agentsare often added either during the production stage or before fillinginto bottles. Generally, there are two types of anti-foam agents, namelysilicones and non-silicones. Silicones are usually aqueous emulsions ofdimethyl polysiloxane, while the non-silicone anti-foam agents arewater-insoluble oils, such as octanol and nonanol, or silica. In bothcases, the function of the anti-foam agent is to displace the surfactantfrom the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce theoverall environmental footprint of crop protection formulations. Greenagents are biodegradable and generally derived from natural and/orsustainable sources, e.g. plant and animal sources. Specific examplesare: vegetable oils, seed oils, and esters thereof, also alkoxylatedalkyl polyglucosides.

Applications

Molecules of Formula One may be applied to any locus. Particular croploci to apply such molecules include loci where alfalfa, almonds,apples, barley, beans, canola, corn, cotton, crucifers, lettuce, oats,oranges, pears, peppers, potatoes, rice, sorghum, soybeans,strawberries, sugarcane, sugar beets, sunflowers, tobacco, tomatoes,wheat, and other valuable crops are growing or the seeds thereof aregoing to be planted.

Molecules of Formula One may also be applied where plants, such ascrops, are growing and where there are low levels (even no actualpresence) of pests that can commercially damage such plants. Applyingsuch molecules in such locus is to benefit the plants being grown insuch locus. Such benefits, may include, but are not limited to: helpingthe plant grow a better root system; helping the plant better withstandstressful growing conditions; improving the health of a plant; improvingthe yield of a plant (e.g. increased biomass and/or increased content ofvaluable ingredients); improving the vigor of a plant (e.g. improvedplant growth and/or greener leaves); improving the quality of a plant(e.g. improved content or composition of certain ingredients); andimproving the tolerance to abiotic and/or biotic stress of the plant.

Molecules of Formula One may be applied with ammonium sulfate whengrowing various plants as this may provide additional benefits.

Molecules of Formula One may be applied on, in, or around plantsgenetically modified to express specialized traits, such as Bacillusthuringiensis or other insecticidal toxins, or those expressingherbicide resistance, or those with “stacked” foreign genes expressinginsecticidal toxins, herbicide resistance, nutrition-enhancement, or anyother beneficial traits.

Molecule of Formula One may be applied to the foliar and/or fruitingportions of plants to control pests. Such molecules will either come indirect contact with the pest, or the pest will consume such moleculeswhen eating the plant or while extracting sap from the plant.

Molecule of Formula One may also be applied to the soil, and whenapplied in this manner, root and stem feeding pests may be controlled.The roots may absorb such molecules thereby taking it up into the foliarportions of the plant to control above ground chewing and sap feedingpests.

Systemic movement of pesticides in plants may be utilized to controlpests on one portion of the plant by applying (for example by spraying alocus) a molecule of Formula One to a different portion of the plant.For example, control of foliar-feeding insects may be achieved by dripirrigation or furrow application, by treating the soil with for examplepre- or post-planting soil drench, or by treating the seeds of a plantbefore planting.

Molecules of Formula One may be used with baits. Generally, with baits,the baits are placed in the ground where, for example, termites can comeinto contact with, and/or be attracted to, the bait. Baits can also beapplied to a surface of a building, (horizontal, vertical, or slantsurface) where, for example, ants, termites, cockroaches, and flies, cancome into contact with, and/or be attracted to, the bait.

Molecules of Formula One may be encapsulated inside, or placed on thesurface of a capsule. The size of the capsules can range from nanometersize (about 100-900 nanometers in diameter) to micrometer size (about10-900 microns in diameter).

Molecules of Formula One may be applied to eggs of pests. Because of theunique ability of the eggs of some pests to resist certain pesticides,repeated applications of such molecules may be desirable to controlnewly emerged larvae.

Molecules of Formula One may be applied as seed treatments. Seedtreatment may be applied to all types of seeds, including those fromwhich plants genetically modified to express specialized traits willgerminate. Representative examples include those expressing proteinstoxic to invertebrate pests, such as Bacillus thuringiensis or otherinsecticidal toxins, those expressing herbicide resistance, such as“Roundup Ready” seed, or those with “stacked” foreign genes expressinginsecticidal toxins, herbicide resistance, nutrition-enhancement,drought resistance, or any other beneficial traits. Furthermore, suchseed treatments with molecules of Formula One may further enhance theability of a plant to better withstand stressful growing conditions.This results in a healthier, more vigorous plant, which can lead tohigher yields at harvest time. Generally, about 1 gram of such moleculesto about 500 grams per 100,000 seeds is expected to provide goodbenefits, amounts from about 10 grams to about 100 grams per 100,000seeds is expected to provide better benefits, and amounts from about 25grams to about 75 grams per 100,000 seeds is expected to provide evenbetter benefits.

Molecules of Formula One may be applied with one or more activeingredients in a soil amendment.

Molecules of Formula One may be used for controlling endoparasites andectoparasites in the veterinary medicine sector or in the field ofnon-human-animal keeping. Such molecules may be applied by oraladministration in the form of, for example, tablets, capsules, drinks,granules, by dermal application in the form of, for example, dipping,spraying, pouring on, spotting on, and dusting, and by parenteraladministration in the form of, for example, an injection.

Molecules of Formula One may also be employed advantageously inlivestock keeping, for example, cattle, sheep, pigs, chickens, salmonand geese. They may also be employed advantageously in pets such as,horses, dogs, and cats. Particular pests to control would be fleas andticks that are bothersome to such animals. Suitable formulations areadministered orally to the animals with the drinking water or feed. Thedosages and formulations that are suitable depend on the species.

Molecules of Formula One may also be used for controlling parasiticworms, especially of the intestine, in the animals listed above.

Molecules of Formula One may also be employed in therapeutic methods forhuman health care. Such methods include, but are limited to, oraladministration in the form of, for example, tablets, capsules, drinks,granules, and by dermal application.

Molecules of Formula One may also be applied to invasive pests. Pestsaround the world have been migrating to new environments (for such pest)and thereafter becoming a new invasive species in such new environment.Such molecules may also be used on such new invasive species to controlthem in such new environments.

Consequently, in light of the above and the Tables in the Table Section,the following items are provided.

1. A molecule having the following formula

wherein:

(A) R¹, R⁵, R⁶, R¹¹, R¹², R¹³, and R¹⁴ are each independently selectedfrom the group consisting of H, F, Cl, Br, I, CN, (C₁-C₄)alkyl,(C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy

preferably, R¹, R⁵, R⁶, R¹¹, R¹², R¹³, and R¹⁴ are H;

(B) R², R³, and R⁴ are each independently selected from the groupconsisting of H, F, Cl, Br, I, CN, (C₁-C₄)alkyl, (C₂-C₄)alkenyl,(C₂-C₄)alkynyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy

preferably, R², R³, and R⁴ are H, F, Cl, Br, CH₃, or CH═CH₂;

(C) R⁷ is (C₁-C₆)haloalkyl

preferably R⁷ is CF₃, CF₂CH₃, or CF₂CH₂CH₃;

(D) R⁹ is selected from the group consisting of (F), H, F, Cl, Br, I,CN, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy

preferably R⁹ is H;

(E) R¹⁰ is selected from the group consisting of (F), F, Cl, Br, I, CN,(C₁-C₄)alkyl, (C₂-C₄)alkenyl, (C₂-C₄)alkynyl, (C₁-C₄)haloalkyl,(C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy

preferably R¹⁰ is Cl, Br, I, CH₃, or CF₃;

(F) R⁹ and R¹⁰ together can optionally form a 3- to 5-membered saturatedor unsaturated, hydrocarbyl link,

wherein said hydrocarbyl link may optionally be substituted with one ormore substituents independently selected from the group consisting of F,Cl, Br, I, and CN;

(G) L is (C₁-C₆)alkyl

preferably L is CH(CH₃) or CH(CH₂CH₃);

(H) X is selected from the group consisting of C, S, and P(C₁-C₆)alkyl

preferably X is C or S;

(I) n is 1 or 2;

(J) R¹⁵ is selected from the group consisting of (C₁-C₄)alkyl,(C₂-C₄)alkenyl, (C₃-C₄)cycloalkyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy,(C₁-C₄)haloalkoxy, phenyl, and NH(C₃-C₄)cycloalkyl,

wherein each alkyl, alkenyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy,and phenyl may optionally be substituted with one or more substituentsindependently selected from the group consisting of F, Cl, Br, I, CN,and OH

preferably R¹⁵ is CH₂CH₃, cyclopropyl, CH₂CF₃, CH₂CH₂CF₃, orNHcyclopropyl; and

agriculturally acceptable acid addition salts, salt derivatives,solvates, ester derivatives, crystal polymorphs, isotopes, resolvedstereoisomers, and tautomers, of the molecules of Formula One.

2. A molecule according to 1 wherein

(A) R¹, R⁵, R⁶, R¹¹, R¹², R¹³, and R¹⁴ are H;

(B) R², R³, and R⁴ are each independently selected from the groupconsisting of H, F, Cl, Br, (C₁-C₄)alkyl, (C₂-C₄)alkenyl;

(C) R⁷ is (C₁-C₆)haloalkyl;

(D) R⁹ is H;

(E) R¹⁹ is selected from the group consisting of Cl, Br, (C₁-C₄)alkyl,and (C₁-C₄)haloalkyl;

(G) L is (C₁-C₆)alkyl;

(H) X is C or S;

(I) n is 1 or 2;

(J) R¹⁵ is selected from the group consisting of (C₁-C₄)alkyl,(C₃-C₄)cycloalkyl, (C₁-C₄)haloalkyl, and NH(C₃-C₄)cycloalkyl,

wherein each alkyl, alkenyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy,and phenyl may optionally be substituted with one or more substituentsindependently selected from the group consisting of F, Cl, Br, I, CN,and OH.

3. A molecule according to 1 wherein said molecule is selected from oneof the molecules in Table 2.4. A molecule according to 1 wherein said molecule is selected from oneof the molecules in Table 1.5. A pesticidal composition comprising a molecule according to any oneof 1, 2, 3, or 4, further comprising one or more active ingredients.6. A pesticidal composition according to 5 wherein said activeingredient is from AIGA.7. A pesticidal composition according to 5 wherein said activeingredient is selected from the group consisting of AI-1,1,3-dichloropropene, chlorpyrifos, chlorpyrifos-methyl, hexaflumuron,methoxyfenozide, noviflumuron, spinetoram, spinosad, sulfoxaflor, andsulfuryl fluoride.8. A pesticidal composition comprising a molecule according to any oneof 1, 2, 3, or 4, further comprising a MoA Material.9. A pesticidal composition according to 7 wherein said MoA Material isfrom MoAMGA.10. A pesticidal composition according to any one of 5, 6, 7, 8, or 9,wherein the weight ratio of the molecule according to Formula One tosaid active ingredient is selected from Table B.11. A process to control a pest said process comprising applying to alocus, a pesticidally effective amount of a molecule according to anyone of the 1, 2, 3, or 4.12. A process to control a pest said process comprising applying to alocus, a pesticidally effective amount of a pesticidal compositionaccording to any one of the 5, 6, 7, 8, 9, or 10.13. A molecule according to any one of 1, 2, 3, or 4, or a pesticidalcomposition according to any of 5, 6, 7, 8, 9, or 10, wherein saidmolecule is in the form of agriculturally acceptable acid addition salt.14. A molecule according to any one of 1, 2, 3, or 4, or a pesticidalcomposition according to any of 5, 6, 7, 8, 9, or 10, wherein saidmolecule is in the form of a salt derivative.15. A molecule according to any one of 1, 2, 3, or 4, or a pesticidalcomposition according to any of 5, 6, 7, 8, 9, or 10, wherein saidmolecule is in the form of solvate.16. A molecule according to any one of 1, 2, 3, or 4, or a pesticidalcomposition according to any of 5, 6, 7, 8, 9, or 10, wherein saidmolecule is in the form of an ester derivative.17. A molecule according to any one of 1, 2, 3, or 4, or a pesticidalcomposition according to any of 5, 6, 7, 8, 9, or 10, wherein saidmolecule is in the form of a crystal polymorph.18. A molecule according to any one of 1, 2, 3, or 4, or a pesticidalcomposition according to any of 5, 6, 7, 8, 9, or 10, wherein saidmolecule has deuterium, tritium, and or ¹⁴C.19. A molecule according to any one of 1, 2, 3, or 4, or a pesticidalcomposition according to any of 5, 6, 7, 8, 9, or 10, wherein saidmolecule is in the form of one or more stereoisomers.20. A molecule according to any one of 1, 2, 3, or 4, or a pesticidalcomposition according to any of 5, 6, 7, 8, 9, or 10, wherein saidmolecule is in the form of a resolved stereoisomer.21. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said pesticidal composition further comprises another activeingredient.22. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said pesticidal composition further comprises two more activeingredients.23. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said active ingredient has a MOA different from the MoA of saidmolecule of Formula One.24. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said pesticidal composition comprises an active ingredienthaving acaricidal, algicidal, avicidal, bactericidal, fungicidal,herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal,and/or virucidal properties.25. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said pesticidal composition comprises an active ingredient thatis an antifeedant, bird repellent, chemosterilant, herbicide safener,insect attractant, insect repellent, mammal repellent, mating disrupter,plant activator, plant growth regulator, and/or synergist.26. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said pesticidal composition comprises an active ingredient thatis a biopesticide.27. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is 100:1 to 1:100.28. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is 50:1 to 1:50.29. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is 20:1 to 1:20.30. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is 10:1 to 1:10.31. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is 5:1 to 1:5.32. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is 3:1 to 1:3.33. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is 2:1 to 1:2.34. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is 1:1.35. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said weight ratio of a molecule of Formula One to an activeingredient is depicted as X:Y; wherein X is the parts by weight of amolecule of Formula One and Y is the parts by weight of activeingredient; further wherein the numerical range of the parts by weightfor X is 0<X≦100 and the parts by weight for Y is 0<Y≦100; and furtherwherein X and Y are selected from Table C.36. A pesticidal composition according to 35 wherein a range of weightratios of a molecule of Formula One to an active ingredient is depictedas X₁: Y₁ to X₂: Y₂; further wherein X₁>Y₁ and X₂<Y₂.37. A pesticidal composition according to 35 wherein a range of weightratios of a molecule of Formula One to an active ingredient is depictedas X₁: Y₁ to X₂: Y₂; further wherein X₁>Y₁ and X₂>Y₂.38. A pesticidal composition according to 35 wherein a range of weightratios of a molecule of Formula One to an active ingredient is depictedas X₁:Y₁ to X₂:Y₂; further wherein X₁<Y₁ and X₂<Y₂.39. A pesticidal composition according to 35 wherein said composition isis synergistic.40. A process according to 12 wherein said pest is from PhylumArthropoda.41. A process according to 12 wherein said pest is from Phylum Mollusca.42. A process according to 12 wherein said pest is from Phylum Nematoda.43. A process according to 12 wherein said pests are are ants, aphids,beetles, bristletails, cockroaches, crickets, earwigs, fleas, flies,grasshoppers, leafhoppers, lice (including sea lice), locusts, mites,moths, nematodes, scales, symphylans, termites, thrips, ticks, wasps,and/or whiteflies.44. A process according to 12 wherein said locus is where alfalfa,almonds, apples, barley, beans, canola, corn, cotton, crucifers,lettuce, oats, oranges, pears, peppers, potatoes, rice, sorghum,soybeans, strawberries, sugarcane, sugar beets, sunflowers, tobacco,tomatoes, wheat, and other valuable crops are growing or the seedsthereof are planted.45. A pesticidal composition according to any of 5, 6, 7, 8, 9, or 10,wherein said pesticidal composition further comprises ammonium sulfate.46. A process according to 12 wherein said locus is where plantsgenetically modified to express specialized traits are planted.47. A process according to 12 wherein said applying is done to thefoliar and/or fruiting portions of plants.48. A process according to 12 wherein said applying is done to the soil.49. A process according to 12 wherein said applying is done by dripirrigation, furrow application, or pre- or post-planting soil drench.50. A process according to 12 wherein said applying is done to thefoliar and/or fruiting portions of plants, or by treating the seeds of aplant before planting.51. A pesticidal composition comprising a molecule according to any oneof 1, 2, 3, or 4, and a seed.52. A process comprising applying a molecule according to any one of 1,2, 3, or 4, or a pesticidal composition according to any of 5, 6, 7, 8,9, or 10, to a seed.53. A process comprising applying a molecule according to 1, 2, 3, or 4,to a locus that includes a non-human animal to control endoparasitesand/or ectoparasites.54. A process to produce a pesticidal composition, said processcomprising mixing a molecule according to any one of claim 1, 2, 3, or4, with one or more active ingredients.

The headings in this document are for convenience only and must not beused to interpret any portion hereof.

Table Section

TABLE 2 Structure and Preparation Method for F Series Molecules No.Structure Prep.* F1 

15 F2 

15 F3 

15 F4 

15 F5 

15 F6 

15 F7 

15 F8 

15 F9 

15 F10

15 F11

14 F12

14 F13

14 F14

14 F15

14 F16

13 F17

14 F18

14 F19

14 F20

15 F21

15 F22

14 F23

14 F24

14 F25

14 F26

14 F27

16 F28

18 F29

19 F30

14 F31

14 F32

14 F33

15 F34

17 F35

17 F36

14 F37

14 F39

16 F40

16 F41

16 *prepared according to example number

TABLE 3 Structure and Preparation Method for C Series Molecules NoStructure Prep.* C1

1 C2

1 C3

1 C4

1 C5

1 C6

1 C7

1 C8

1 C9

1 C10

1 C11

1 C12

1 C13

1 C14

1 C15

1 C16

1 C17

1 C18

1 C19

1 C20

1 C21

2 C22

3 C23

4 C24

5 C25

5, 7 C26

5 C27

5, 7 C28

6 C29

6 C30

6 C31

6 C32

7 C33

7 C34

8 C35

8 C36

8 C37

8 C38

8 C39

8 C40

8 C41

8 C42

9 C43

10 C44

10 C45

10 C46

11 C47

11 C48

11 C49

11 C50

11 C51

11 C52

12 C53

12 C54

12 C55

20 C56

20 C57

21 C58

21 C59

22 C60

22 C61

23 C62

23 C63

1 C64

1 C65

1 C66

7 C67

8 C68

11 C69

24 C70

8 C71

10 C72

25 *prepared according to example number

TABLE 4 Analytical Data for Molecules in Table 2 Mp ¹³C NMR; No. (° C.)Mass (m/z) ¹H NMR ¹⁹F NMR; IR F1 663 ¹H NMR (400 MHz, ¹⁹F NMR (376 ([M +H]⁺) CDCl₃) δ 7.81 (d, MHz, CDCl₃) δ J = 1.6 Hz, 1H), −59.30, −66.87,7.71 (dd, J = 8.1, −69.36 (d, J = 2.2 1.7 Hz, 1H), 7.49 Hz), −112.02 (t,(d, J = 8.1 Hz, J = 14.4 Hz) 1H), 7.43 (s, 2H), 7.29 (s, 1H), 7.17 (d, J= 7.6 Hz, 1H), 5.81 (dd, J = 32.6, 9.6 Hz, 1H), 5.47 (q, J = 7.2 Hz,1H), 4.60 (p, J = 8.8 Hz, 1H), 2.46-2.27 (m, 4H), 1.65 (d, J = 6.8 Hz,3H) F2 609 ¹H NMR (400 MHz, ¹⁹F NMR (376 ([M + H]⁺) CDCl₃) δ 7.42 (s,MHz, CDCl₃) δ 2H), 7.34 (s, 1H), −66.80, −69.48, 7.30 (d, J = 2.6−111.78 Hz, 2H), 7.28 (s, 1H), 5.69 (dd, J = 32.9, 9.6 Hz, 1H), 5.58 (p,J = 7.1 Hz, 1H), 4.57 (p, J = 8.9 Hz, 1H), 2.45-2.29 (m, 7H), 1.61 (d, J= 6.7 Hz, 3H) F3 671 ¹H NMR (400 MHz, ¹⁹F NMR (376 ([M − H]⁻) CDCl₃) δ7.70 (d, MHz, CDCl₃) δ J = 7.9 Hz, 1H), −66.81, −67.67- 7.64 (d, J = 1.6−72.15 (m), Hz, 1H), 7.52- −112.14 7.44 (m, 1H), 7.41 (d, J = 3.1 Hz,3H), 7.36 (d, J = 8.1 Hz, 1H), 5.84-5.56 (m, 2H), 4.56 (p, J = 8.9 Hz,1H), 2.51- 2.15 (m, 4H), 1.63-1.53 (m, 3H) F4 657 ¹H NMR (400 MHz, ¹⁹FNMR (376 ([M − H]⁻) CDCl₃) δ 8.25 (d, MHz, CDCl₃) δ J = 8.5 Hz, 1H),−62.97, −68.04- 8.22-8.07 (m, −70.81 (m), 1H), 7.41 (d, J = −112.29 2.0Hz, 2H), 7.25 (d, J = 9.5 Hz, 1H), 7.16 (dd, J = 7.8, 1.5 Hz, 1H), 5.93(q, J = 7.9 Hz, 1H), 5.67 (ddd, J = 32.7, 9.6, 4.8 Hz, 1H), 4.52 (p, J =8.9 Hz, 1H), 3.25- 2.86 (m, 2H), 1.52 (d, J = 6.6 Hz, 3H) F5 649 ¹H NMR(400 MHz, ¹⁹F NMR (376 ([M + H]⁺) CDCl₃) δ 8.44 (s, MHz, CDCl₃) δ 1H),8.29 (s, 1H), −59.85, −63.33 (d, 7.50 (dd, J = 3.8, J = 2.4 Hz), 1.7 Hz,1H), 7.47- −69.48, −110.42- 7.33 (m, 3H), −114.23 (m) 7.17 (d, J = 7.9Hz, 1H), 5.95 (d, J = 7.9 Hz, 1H), 5.71 (ddd, J = 32.6, 9.6, 5.6 Hz,1H), 4.54 (p, J = 8.9 Hz, 1H), 3.04 (dd, J = 15.4, 10.1 Hz, 1H), 2.90(t, J = 12.4 Hz, 1H), 1.41 (d, J = 6.5 Hz, 3H) F6 591 ¹H NMR (400 MHz,¹⁹F NMR (376 ([M + H]⁺) CDCl₃) δ 8.06 (d, MHz, CDCl₃) δ - J = 7.3 Hz,1H), −63.07, −94.11- 7.90 (s, 1H), 7.42 −96.32 (m), (d, J = 1.3 Hz,−114.28 2H), 7.18 (s, 1H), 7.16-7.07 (m, 2H), 5.88-5.63 (m, 2H), 4.25(td, J = 14.2, 9.7 Hz, 1H), 3.18-3.02 (m, 1H), 2.93 (m, 1H), 2.12 (s,3H), 1.64 (t, J = 18.4 Hz, 3H), 1.51 (d, J = 6.6 Hz, 3H) F7 615 ¹H NMR(400 MHz, ¹⁹F NMR (376 ([M + H]⁺) CDCl₃) δ 8.41 (d, MHz, CDCl₃) δ J =8.6 Hz, 1H), −63.05, −69.49, 8.27 (d, J = 8.2 −112.31 Hz, 1H), 7.40 (d,J = 1.7 Hz, 2H), 7.27 (d, J = 1.3 Hz, 1H), 7.21 (t, J = 5.4 Hz, 2H),5.98 (q, J = 7.9 Hz, 1H), 5.68 (ddd, J = 32.7, 9.6, 4.5 Hz, 1H), 4.53(p, J = 8.9 Hz, 1H), 3.24- 2.87 (m, 2H), 1.49 (d, J = 6.5 Hz, 3H) F8 645¹H NMR (400 MHz, ¹⁹F NMR (376 ([M + H]⁺) CDCl₃) δ 7.83 (s, MHz, CDCl₃)δ - 1H), 7.74 (d, J = −59.43, −63.18, 8.6 Hz, 1H), 7.51 −93.17-−97.04,(d, J = 8.1 Hz, −114.80 1H), 7.42 (s, 2H), 6.99 (d, J = 7.4 Hz, 1H),6.85 (d, J = 7.4 Hz, 1H), 5.88 (dd, J = 33.8, 9.8 Hz, 1H), 5.46 (q, J =7.1 Hz, 1H), 4.27 (td, J = 14.3, 9.7 Hz, 1H), 3.06 (q, J = 10.4 Hz, 2H),1.71 (d, J = 6.8 Hz, 3H), 1.62 (d, J = 18.5 Hz, 3H) F9 629 ¹H NMR (400MHz, ¹⁹F NMR (376 ([M + H]⁺) CDCl₃) δ 7.83 (d, MHz, CDCl₃) δ J = 7.9 Hz,1H), −66.84, −69.44 (d, 7.54-7.48 (m, J = 2.4 Hz), 1H), 7.47-7.43−110.87-−113.41 (m, 2H), 7.41 (s, (m) 2H), 7.40-7.35 (m, 1H), 5.81- 5.61(m, 2H), 4.56 (p, J = 8.9 Hz, 1H), 2.46- 2.14 (m, 4H), 1.57 (d, J = 6.6Hz, 3H) F10 659 ¹H NMR (400 MHz, ¹³C NMR (101 ([M + H]⁺) CDCl₃) δ 8.05(d, MHz, CDCl₃) δ J = 8.1 Hz, 1H), 169.85, 166.53, 7.83 (t, J = 5.8161.53-153.79 Hz, 1H), 7.67- (m), 136.96, 7.60 (m, 1H), 135.96, 134.51,7.52 (d, J = 8.2 132.74, 131.21, Hz, 1H), 7.41 (s, 129.10, 128.60, 2H),7.33-7.24 127.91, 127.29, (m, 1H), 5.96- 125.17, 122.19, 5.69 (m, 2H),103.44 (d, J = 4.33-4.15 (m, 16.0 Hz), 99.98, 1H), 2.35-2.05 53.81-52.37(m, 4H), 1.71- (m), 48.64- 1.57 (m, 3H), 47.20 (m), 29.79- 1.45 (d, J =6.6 28.88 (m), Hz, 3H) 28.27, 23.34- 21.75 (m), 19.91 F11 613 ¹H NMR(400 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.98 3239, 2928, (d, J =7.2 Hz, 1674, 1119 cm⁻¹ 1H), 8.66 (d, J = 6.8 Hz 1H), 8.11 (s, 1H), 8.05(d, J = 8.0 Hz, 1H), 7.81 (s, 2H), 7.68 (s, 1H), 7.56 (d, J = 7.6 Hz,1H), 6.84 (dd, J = 35.6, 9.6 Hz, 1H), 5.60-5.55 (m, 1H), 5.23-5.18 (m,1H), 3.31- 3.22 (m, 2H), 1.36 (d, J = 6.4 Hz, 3H) F12 627 ¹H NMR (400MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.85 3439, 3300, (d, J = 6.8Hz, 1669, 749 cm⁻¹ 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.10 (s, 1H), 8.04 (d,J = 8.0 Hz, 1H), 7.81 (s, 2H), 7.68 (s, 1H), 7.57 (d, J = 8.4 Hz, 1H),6.84 (dd, J = 36.0, 10.4 Hz, 1H), 5.60-5.55 (m, 1H), 5.23- 5.18 (m, 1H),2.50-2.33 (m, 4H), 1.34 (d, J = 6.4 Hz, 3H) F13 613 ¹H NMR (400 MHz, IR(thin film) ([M + H]⁺) DMSO-d₆) δ 8.98 3439, 3302, (d, J = 7.6 Hz, 1676,750 cm⁻¹ 1H), 8.66 (d, J = 8.0 Hz, 1H), 8.11 (s, 1H), 8.05- 8.03 (m,1H), 8.00 (s, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.68-7.65 (m, 1H), 7.56 (d,J = 8.0 Hz, 1H), 6.83 (dd, J = 36.0, 10.4 Hz, 1H), 5.60-5.55 (m, 1H),5.20- 5.15 (m, 1H), 3.31-3.22 (m, 2H), 1.34 (d, J = 6.8 Hz, 3H) F14 627¹H NMR (400 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.85 3439, 3300,1669, (d, J = 6.8 Hz, 749 cm⁻¹ 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.10 (s,1H), 8.04- 7.99 (m, 2H), 7.74 (d, J = 8.4 Hz, 1H), 7.72- 7.65 (m, 1H),7.56 (d, J = 8.0 Hz, 1H), 6.84 (dd, J = 35.6, 10.0 Hz, 1H), 5.60-5.55(m, 1H), 5.20- 5.15 (m, 1H), 2.51-2.33 (m, 4H), 1.34 (d, J = 6.4 Hz, 3H)F15 705 ¹H NMR (300 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.86 3423,1667 cm⁻¹ (d, J = 7.2 Hz, 1H), 8.43 (d, J = 7.2 Hz, 1H), 8.09 (s, 1H),8.04- 8.00 (m, 3H), 7.57 (d, J = 8.1 Hz, 1H), 6.86 (dd, J = 35.7, 9.9Hz, 1H), 5.61-5.54 (m, 1H), 5.25- 5.19 (m, 1H), 2.50-2.30 (m, 4H), 1.34(d, J = 6.6 Hz, 3H) F16 631 ¹H NMR (400 MHz, IR (thin film) ([M + H]⁺)DMSO-d₆) δ 8.95 3302, 1672, (d, J = 7.2 Hz, 1120, 714 cm⁻¹ 1H), 8.64 (d,J = 7.2 Hz, 1H), 8.09 (s, 1H), 8.05 (d, J = 7.6 Hz, 1H), 7.99 (d, J =6.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 1H), 6.82 (dd, J = 35.6, 10.4 Hz, 1H),5.61-5.55 (m, 1H), 5.23- 5.22 (m, 1H), 3.30-3.22 (m, 2H), 1.36 (d, J =6.4 Hz, 3H) F17 645 ¹H NMR (300 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆)δ 8.86 3741, 3309, (d, J = 6.9 Hz, 2935, 1670, 1132 1H), 8.43 (d, J =cm⁻¹ 7.2 Hz, 1H), 8.09 (s, 1H), 8.04 (s, 1H), 8.00 (d, J = 6.3 Hz, 2H),7.57 (d, J = 7.8 Hz, 1H), 6.84 (dd, J = 36.0, 10.2 Hz, 1H), 5.61-5.54(m, 1H), 5.24- 5.23 (m, 1H), 2.45-2.30 (m, 4H), 1.34 (d, J = 6.6 Hz, 3H)F18 98- 639 ¹H NMR (300 MHz, 100 ([M + H]⁺) CDCl₃) δ 7.84 (s, 1H), 7.79(d, J = 8.1 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.43 (s, 1H), 7.36 (s,1H), 6.81- 6.72 (m, 1H), 5.94-5.65 (m, 3H), 5.49-5.31 (m, 1H), 4.64-4.60 (m, 1H), 3.12 (q, J = 10.5 Hz, 2H), 1.72 (d, J = 6.9 Hz, 3H) F1956- 653 ¹H NMR (300 MHz, 58 ([M + H]⁺) CDCl₃) δ 7.85 (s, 1H), 7.79 (d, J= 8.1 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.43 (s, 1H), 7.37 (s, 1H),7.01- 6.92 (dd, J = 17.7, 11.4 Hz, 1H), 5.94-5.65 (m, 3H), 5.47- 5.31(m, 1H), 4.67-4.60 (m, 1H), 2.50-2.43 (m, 4H), 1.70 (d, J = 6.9 Hz, 3H)F20 659 ¹H NMR (400 MHz, ¹⁹F NMR (471 ([M + H]⁺) CDCl₃) δ 7.81 (s, MHz,CDCl₃) δ - 1H), 7.72 (d, J = −59.15, −63.05, 8.0 Hz, 1H), 7.48−102.66-−106.98 (d, J = 8.0 Hz, (m), −114.95 1H), 7.41 (s, 2H), 7.21 (s,1H), 6.99 (s, 1H), 6.00- 5.78 (m, 1H), 5.44 (h, J = 7.0 Hz, 1H), 4.30(td, J = 14.5, 9.8 Hz, 1H), 3.06 (q, J = 10.4 Hz, 2H), 1.94- 1.79 (m,2H), 1.70 (d, J = 6.8 Hz, 3H), 1.07 (t, J = 7.5 Hz, 3H) F21 673 ¹H NMR(400 MHz, ¹⁹F NMR (471 ([M + H]⁺) CDCl₃) δ d 7.80 (s, MHz, CDCl₃) δ-¹⁹F1H), 7.70 (dd, J = NMR (471 MHz, 8.2, 2.8 Hz, 1H), CDCl₃) δ −59.15, 7.48(dd, J = 8.1, −66.78, −102.42- 3.6 Hz, 1H), 7.41 −107.74 (m), (s, 2H),7.07 (s, −115.03 2H), 5.88 (ddd, J = 33.9, 9.7, 3.3 Hz, 1H), 5.50- 5.37(m, 1H), 4.30 (td, J = 14.6, 9.8 Hz, 1H), 2.41 (br s, 4H), 2.00- 1.78(m, 2H), 1.70-1.63 (m, 3H), 1.07 (t, J = 7.4 Hz, 3H) F22 135- 699 ¹H NMR(300 MHz, 137 ([M − H]⁻) DMSO-d₆) δ 8.98 (d, J = 7.5 Hz, 1H), 8.66 (d, J= 7.2 Hz, 1H), 8.11 (s, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.96 (s, 2H),7.90 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 6.86 (dd, J = 35.7, 9.9 Hz, 1H),5.61-5.54 (m, 1H), 5.22-5.21 (m, 1H), 3.28- 3.21 (m, 2H), 1.36 (d, J =6.3 Hz, 3H) F23 130- 713 ¹H NMR (300 MHz, 132 ([M − H]⁻) DMSO-d₆) δ 8.86(d, J = 6.9 Hz, 1H), 8.43 (d, J = 7.5 Hz, 1H), 8.10 (s, 1H), 8.05 (d, J= 8.1 Hz, 1H), 7.96 (s, 2H), 7.91- 7.90 (m, 1H), 7.57 (d, J = 8.1 Hz,1H), 6.86 (dd, J = 36.0, 10.2 Hz, 1H), 5.59-5.54 (m, 1H), 5.22- 5.21 (m,1H), 2.43-2.32 (m, 4H), 1.34 (d, J = 6.6 Hz, 3H) F24 605 ¹H NMR (300MHz, IR (thin film) ([M − H]⁻) DMSO-d₆) δ 8.97 3423, 2924, (d, J = 7.2Hz, 1674, 714 cm⁻¹ 1H), 8.66 (d, J = 6.9 Hz, 1H), 8.07 (s, 1H), 8.05 (d,J = 8.1 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.45 (s, 2H), 6.77 (dd, J =35.4, 9.6 Hz, 1H), 5.59-5.56 (m, 1H), 4.95-4.85 (m, 1H), 3.31- 3.21 (m,2H), 2.36 (s, 6H), 1.36 (d, J = 8.1 Hz, 3H) F25 619 ¹H NMR (300 MHz, IR(thin film) ([M − H]⁻) DMSO-d₆) δ 8.85 3308, 2925, 1668 (d, J = 6.9 Hz,cm⁻¹ 1H), 8.42 (d, J = 7.2 Hz, 1H), 8.06 (s, 1H), 8.04 (d, J = 8.1 Hz,1H), 7.56 (d, J = 8.1 Hz, 1H), 7.45 (s, 2H), 6.77 (dd, J = 36.3, 10.2Hz, 1H), 5.58-5.56 (m, 1H), 4.95- 4.88 (m, 1H), 2.50-2.40 (m, 4H), 2.35(s, 6H), 1.29-1.21 (d, J = 6.9 Hz, 3H) F26 733 ¹H NMR (300 MHz, IR (thinfilm) ([M − H]⁻) DMSO-d₆) δ 8.98 3308, 1674 cm⁻¹ (d, J = 7.2 Hz, 1H),8.67 (d, J = 7.2 Hz, 1H), 8.17- 8.03 (m, 4H), 7.57 (d, J = 8.1 Hz, 1H),6.86 (dd, J = 35.7, 10.2 Hz, 1H), 5.61-5.54 (m, 1H), 5.25- 5.19 (m, 1H),3.31-3.21 (m, 2H), 1.36 (d, J = 6.3 Hz, 3H) F27 605 ¹H NMR (500 MHz, ¹⁹FNMR (471 ([M − H]⁻) CDCl₃) δ 7.87- MHz, CDCl₃) δ 7.82 (m, 1H), −59.18,−69.32 (d, 7.74 (dd, J = 8.1, J = 8.4 Hz), 1.7 Hz, 1H), 7.54 −111.89 (d,J = (d, J = 8.1 Hz, 32.5 Hz) 1H), 7.43 (s, 2H), 7.01 (d, J = 7.3 Hz,1H), 6.80 (d, J = 7.6 Hz, 1H), 5.81 (dd, J = 32.5, 9.6 Hz, 1H), 5.42 (h,J = 7.0 Hz, 1H), 4.60 (p, J = 8.9 Hz, 1H), 1.70 (d, J = 6.7 Hz, 3H),1.36 (tt, J = 7.9, 4.6 Hz, 1H), 1.00-0.86 (m, 2H), 0.77 (dt, J = 7.9,3.4 Hz, 2H) F28 150- 683 ¹H NMR (300 MHz, 152 ([M − H]⁻)Acetonitrile-d₃) δ 8.10-8.01 (m, 1H), 7.94 (dd, J = 8.1, 1.8 Hz, 1H),7.71 (s, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.62-7.56 (m, 1H), 6.27 (dd, J =34.2, 9.8 Hz, 1H), 5.51 (dq, J = 7.9, 6.6 Hz, 1H), 4.91 (p, J = 9.2 Hz,1H), 4.41- 4.13 (m, 2H), 1.50 (d, J = 6.6 Hz, 3H) F29 158- 620 ¹H NMR(300 MHz, 162 ([M − H]⁻) Acetonitrile-d₃) δ 7.91 (d, J = 1.7 Hz, 1H),7.85- 7.77 (m, 1H), 7.70 (s, 2H), 7.59 (d, J = 7.8 Hz, 1H), 7.46 (d, J =8.1 Hz, 1H), 6.22 (dd, J = 34.2, 9.8 Hz, 1H), 5.91 (d, J = 8.4 Hz, 1H),5.80-5.69 (m, 1H), 5.69-5.55 (m, 1H), 4.88 (p, J = 9.1 Hz, 1H), 2.42(dtd, J = 9.2, 6.6, 3.6 Hz, 1H), 1.43 (d, J = 6.5 Hz, 3H), 0.74- 0.52(m, 2H), 0.51-0.29 (m, 2H) F30 749 ¹H NMR (300 MHz, IR (thin film) ([M +H]⁺) DMSO-d₆) δ 8.86 3320, 2925, (d, J = 6.9 Hz, 1663, 1138 cm⁻¹ 1H),8.43 (d, J = 7.5 Hz, 1H), 8.17 (s, 2H), 8.10- 7.96 (m, 2H), 7.57 (d, J =8.1 Hz, 1H), 6.86 (dd, J = 36.0, 10.5 Hz, 1H), 5.59-5.56 (m, 1H), 5.22-5.19 (m, 1H), 2.45-2.32 (m, 4H), 1.34 (d, J = 6.6 Hz, 3H) F31 691 ¹H NMR(300 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.98 3302, 1678, 1119 (d,J = 7.5 Hz, cm⁻¹ 1H), 8.67 (d, J = 7.2 Hz, 1H), 8.11- 8.00 (m, 4H), 7.57(d, J = 8.1 Hz, 1H), 6.86 (dd, J = 36.3, 10.2 Hz, 1H), 5.61-5.56 (m,1H), 5.25- 5.19 (m, 1H), 3.31-3.21 (m, 2H), 1.37 (d, J = 6.6 Hz, 3H F32701 ¹H NMR (400 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.97 3415,2925, (d, J = 7.6 Hz, 1663, 1114 cm⁻¹ 1H), 8.66 (d, J = 7.2 Hz, 1H),8.11 (s, 2H), 8.05 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.62-7.59 (m, 1H), 7.56 (d, J = 7.6 Hz, 1H), 6.82 (dd, J = 36.0, 9.6 Hz, 1H),5.60-5.55 (m, 1H), 5.18- 5.13 (m, 1H), 3.31-3.22 (m, 2H), 1.36 (d, J =6.4 Hz, 3H) F33 615 ¹H NMR (400 MHz, ¹⁹F NMR (376 ([M + Na]⁺) CDCl₃) δ8.26 (dd, MHz, CDCl₃) δ J = 39.4, 8.3 Hz, −63.18 (d, J = 54.7 2H), 7.41(s, 2H), Hz), −69.55 (d, 7.14 (d, J = 19.5 J = 2.9 Hz), Hz, 3H), 5.94(q, −111.92 (d, J = J = 7.5 Hz, 1H), 39.2 Hz); 5.65 (ddd, J = IR (thinfilm) 32.9, 9.6, 2.1 Hz, 3291, 1673, 1H), 4.55 (p, J = 1112, 727 cm⁻¹8.8 Hz, 1H), 3.25- 3.04 (m, 1H), 2.97 (p, J = 10.5 Hz, 1H), 2.11 (s,3H), 1.48 (d, J = 6.6 Hz, 3H) F34 593 ¹H NMR (400 MHz, ¹⁹F NMR (376 ([M− H]⁻) CDCl₃) δ 7.87- MHz, CDCl₃) δ 7.79 (m, 1H), −59.21, −69.32, 7.74(dd, J = 8.1, −111.91 1.7 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.43 (s,2H), 7.05 (d, J = 7.2 Hz, 1H), 6.65 (d, J = 7.6 Hz, 1H), 5.81 (dd, J =32.5, 9.6 Hz, 1H), 5.42 (h, J = 7.0 Hz, 1H), 4.60 (p, J = 8.9 Hz, 1H),2.21 (q, J = 7.6 Hz, 2H), 1.69 (d, J = 6.7 Hz, 3H), 1.13 (t, J = 7.6 Hz,3H) F35 661 ¹H NMR (400 MHz, ¹⁹F NMR (376 ([M − H]⁻) CDCl₃) δ 7.76- MHz,CDCl₃) δ 7.51 (m, 3H), −59.52, −63.24, 7.42 (s, 2H), 7.36 −69.39,−112.22 (d, J = 8.1 Hz, 1H), 5.76 (ddd, J = 32.6, 9.6, 2.1 Hz, 1H), 5.39(q, J = 8.3 Hz, 1H), 4.57 (p, J = 8.8 Hz, 1H), 3.02 (dtt, J = 20.8,15.0, 10.5 Hz, 2H), 1.91 (q, J = 7.5 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H)F36 657 ¹H NMR (300 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.98 3297,2919, (d, J = 7.2 Hz, 1674, 1118 cm⁻¹ 1H), 8.66 (d, J = 7.8 Hz, 1H),8.11- 8.03 (m, 2H), 7.93 (s, 1H), 7.84- 7.79 (m, 2H), 7.57 (d, J = 7.8Hz, 1H), 6.86 (dd, J = 35.7, 9.9 Hz, 1H), 5.61-5.54 (m, 1H), 5.23- 5.16(m, 1H), 3.31-3.19 (m, 2H), 1.36 (d, J = 6.6 Hz, 3H) F37 657 ¹H NMR (400MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.98 3330, 1673, 1132 (d, J =7.2 Hz, cm⁻¹ 1H), 8.66 (d, J = 7.2 Hz, 1H), 8.11 (s, 2H), 8.05 (d, J =8.0 Hz, 1H), 7.73-7.68 (m, 2H), 7.56 (d, J = 8.4 Hz, 1H), 6.83 (dd, J =35.6, 9.6 Hz, 1H), 5.60- 5.55 (m, 1H), 5.20-5.15 (m, 1H), 3.31-3.22 (m,2H), 1.36 (d, J = 6.8 Hz, 3H) F39 609.4 ¹H NMR (400 MHz, ¹⁹F NMR (376([M + H]⁺) CDCl₃) δ 7.82 (s, MHz, CDCl₃) δ 1H), 7.72 (d, J = −59.20,−63.09, 7.9 Hz, 1H), 7.51- −90.39-−101.60 7.47 (m, 2H), (m), −115.427.45 (d, J = 8.3 Hz, 1H), 7.23 (dd, J = 8.3, 1.7 Hz, 1H), 7.08 (d, J =7.5 Hz, 1H), 6.89 (d, J = 7.4 Hz, 1H), 5.92 (dd, J = 33.9, 9.8 Hz, 1H),5.53-5.37 (m, 1H), 4.30 (td, J = 14.2, 9.7 Hz, 1H), 3.06 (q, J = 10.4Hz, 2H), 1.74- 1.57 (m, 6H) F40 623.4 ¹H NMR (400 MHz, ¹⁹F NMR (376 (M +H]⁺) CDCl₃) δ 7.82 (s, MHz, CDCl₃) δ 1H), 7.73 (d, J = −59.12, −66.80,8.1 Hz, 1H), 7.56- −93.09-−97.12 7.42 (m, 3H), (m), −115.40 7.23 (d, J =8.4 Hz, 1H), 6.79 (d, J = 7.3 Hz, 1H), 6.67 (d, J = 7.6 Hz, 1H), 5.92(dd, J = 34.0, 9.8 Hz, 1H), 5.50-5.36 (m, 1H), 4.39- 4.20 (m, 1H),2.54-2.37 (m, 4H), 1.69 (d, J = 6.8 Hz, 3H), 1.62 (t, J = 18.4 Hz, 3H)F41 620 ¹H NMR (500 MHz, ¹⁹F NMR (471 ([M + H]⁺) CDCl₃) δ 7.77 (s, MHz,CDCl₃) δ 1H), 7.70-7.66 −59.24, −69.35 (m, 1H), 7.48 (d, (d, J = 8.6Hz), J = 8.1 Hz, 1H), −112.20 (dd, J = 7.47-7.40 (m, 32.7, 7.5 Hz) 4H),5.81 (dd, J = 32.6, 9.6 Hz, 1H), 5.53 (h, J = 7.1 Hz, 1H), 4.59 (p, J =8.9 Hz, 1H), 2.61-2.49 (m, 4H), 1.61 (d, J = 6.7 Hz, 3H)

TABLE 5 Structure and Preparation Method for FC Series Compounds No.Structure Prep.* FC1

15 FC2

15 *prepared according to example number

TABLE 6 Structure and Preparation Method for CC Series Molecules No.Structure Prep.* CC1

1 *prepared according to example number

TABLE 7 Analytical Data for Compounds in Table 5 Mp Mass ¹³C NMR; No. (°C.) (m/z) ¹H NMR ¹⁹F NMR; IR FC1 581 ¹H NMR (300 MHz, ¹⁹F NMR (471 ([M +H]⁺) CDCl₃) δ 7.79 (d, J = MHz, CDCl₃) δ 8.3 Hz, 2H), 7.62 (d, −63.01,−63.03, J = 8.5 Hz, 2H), 7.43 −63.05, −69.39, (s, 2H), 7.30 (d, J =−69.40, −111.70, 7.7 Hz, 1H), 7.08 (d, −111.77 J = 7.4 Hz, 1H), 5.78(dd, J = 32.7, 9.6 Hz, 1H), 5.52 (q, J = 7.1 Hz, 1H), 4.59 (p, J = 9.0Hz, 1H), 3.05 (q, J = 10.4 Hz, 2H), 1.73 (d, J = 6.8 Hz, 3H) FC2 595 ¹HNMR (300 MHz, ¹⁹F NMR (471 ([M + H]⁺) CDCl₃) δ 7.80 (d, J = MHz, CDCl₃)δ 8.1 Hz, 2H), 7.65 −66.75, −66.76, 7.57 (m, 2H), 7.51 (d, −66.77,−66.80, J = 7.4 Hz, 1H), 7.43 −69.40, −69.42, (s, 2H), 7.06 (d, J =−111.72, −111.79 7.5 Hz, 1H), 5.78 (dd, J = 32.8, 9.6 Hz, 1H), 5.52 (h,J = 7.0 Hz, 1H), 4.59 (p, J = 8.9 Hz, 1H), 2.56 2.39 (m, 3H), 1.70 (d, J= 6.8 Hz, 3H)

TABLE 8 Structure and Preparation Method for PF Series Molecules No.Structure Prep.* PF1

14 PF2

14 PF3

14 PF4

14 PF8

14 PF13

14 PF31

16 *prepared according to example number

TABLE 9 Analytical Data for Molecules in Table 8 Mp Mass ¹³C NMR; No. (°C.) (m/z) ¹H NMR ¹⁹F NMR; IR PF1 629.06 ¹H NMR (300 MHz, IR (thin film)([M + H]⁺) DMSO-d₆) δ 9.02 (d, 3310, 1671, J = 7.8 Hz, 1H), 8.72 1114,765 cm⁻¹ (d, J = 6.9 Hz, 1H), 8.21 (d, J = 6.9 Hz, 1H), 8.07 (s, 2H),7.97 (d, J = 6.3 Hz, 1H), 7.73-7.68 (m, 1H), 7.65 (s, 2H), 7.58 (d, J =7.2 Hz, 1H), 6.29 (dd, J = 10.2, 33.9 Hz, 1H), 5.75-5.70 (m, 1H),5.35-5.28 (m, 1H), 3.30-3.25 (m, 2H), 1.42 (d, J = 6.3 Hz, 3H) PF2595.30 ¹H NMR (400 MHz, IR (thin film) ([M − H]⁻) DMSO-d₆) δ 8.98 (d,3432, 2925, J = 7.2 Hz, 1H), 8.66 1673 cm⁻¹ (d, J = 7.2 Hz, 1H), 8.11(s, 1H), 8.05 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 10.4 Hz, 1H), 7.71 (d, J= 8.0 Hz, 1H), 7.56-7.53 (m, 2H), 6.80 (dd, J = 10.0, 36.0 Hz, 1H),5.59-5.57 (m, 1H), 5.17-5.15 (m, 1H), 3.31-3.22 (m, 2H), 1.36 (d, J =6.4 Hz, 3H) PF3 611.14 ¹H NMR (400 MHz, IR (thin film) ([M + H]⁺)DMSO-d₆) δ 8.85 3429, 2916, (d, J = 7.2 Hz, 1H), 1652, 1025 cm⁻¹ 8.42(d, J = 7.2 Hz, 1H), 8.10 (s, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.96 (d, J= 6.8 Hz, 1H), 7.68 (s, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.8Hz, 1H), 6.82 (dd, J = 10.0, 36.0 Hz, 1H), 5.60-5.55 (m, 1H), 5.18-5.13(m, 1H), 2.41-2.33 (m, 4H), 1.34 (d, J = 8.0 Hz, 3H) PF4 627.00 ¹H NMR(300 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆) δ 8.98 3309, 2926, (d, J =7.2 Hz, 1H), 1678 cm⁻¹ 8.66 (d, J = 7.2 Hz, 1H), 8.09 (s, 1H), 8.07 (d,J = 6.0 Hz, 1H), 7.83 (s, 1H), 7.64 (s, 1H), 7.51 (d, J = 8.1 Hz, 1H),6.82 (dd, J = 9.9, 35.4 Hz, 1H), 5.61-5.54 (m, 1H), 5.12-5.05 (m, 1H),3.31-3.21 (m, 2H), 2.49 (s, 3H), 1.39 (d, J = 6.0 Hz, 3H) PF8 84-86659.20 ¹H NMR (300 MHz, ([M + H]⁺) DMSO-d₆) δ 8.98 (d, J = 7, 2 Hz, 1H),8.66 (d, J = 7.5 Hz, 1H), 8.11 (s, 1H), 8.05- 7.98 (m, 2H), 7.87 (d, J =8.4 Hz, 1H), 7.58 (t, J = 6.0 Hz, 2H), 6.84-6.69 (dd, J = 9.9 Hz, 1H),5.61- 5.54 (m, 1H) 5.19- 5.13 (m, 1H), 3.31 (s, 2H), 1.36 (d, J = 6.0Hz, 3H) PF13 671.10 ¹H NMR (300 MHz, IR (thin film) ([M + H]⁺) DMSO-d₆)δ 8.85 (d, 3284, 2925, J = 6.9 Hz, 1H), 8.42 1665, 1136 cm⁻¹ (d, J = 7.2Hz, 1H), 8.11-8.10 (m, 2H), 8.04 (d, J = 8.4 Hz, 1H), 7.71 (s, 2H), 7.56(d, J = 8.1 Hz, 1H), 6.84 (dd, J = 9.9, 36.0 Hz, 1H), 5.61-5.54 (m, 1H),5.20-5.14 (m, 1H), 2.50-2.32 (m, 4H), 1.34 (d, J = 6.6 Hz, 3H) PF31630.7 ¹H NMR (500 MHz, ¹⁹F NMR (471 ([M − H]⁻) CDCl₃) δ 7.83 (d, J =MHz, CDCl₃) δ 1.7 Hz, 1H), 7.75 −59.02, −69.32 (dd, J = 8.1, 1.7 Hz, (d,J = 8.6 Hz), 1H), 7.56 (d, J = 8.0 −111.99 (dd, J = Hz, 1H), 7.44 (s,2H) 32.5, 7.2 Hz) 7.33 (d, J = 7.1 Hz, 1H), 6.80 (d, J = 7.9 Hz, 1H),5.82 (dd, J = 32.5, 9.6 Hz, 1H), 5.64 (h, J = 6.9 Hz, 1H), 4.68-4.55 (m,1H), 1.72-1.65 (m, 4H), 1.57-1.49 (m, 2H), 1.26 (t, J = 7.2 Hz, 1H)

BAW, CEW & CL Rating Table % Control (or Mortality) Rating 50-100 A Morethan 0-Less than 50 B Not Tested C No activity noticed in this bioassayD

GPA & YFM Rating Table % Control (or Mortality) Rating 80-100 A Morethan 0-Less than 80 B Not Tested C No activity noticed in this bioassayD

TABLE ABC Biological Results Pests No. BAW CL GPA YFM F1 A A C C F2 A AC C F3 A A C C F4 A A C C F5 A A C C F6 A A C C F7 A A C C F8 A A C C F9A A C C F10 A A C C F11 A A C A F12 A A C A F13 A A C A F14 A A C A F15A A C A F16 A A C B F17 A A B A F18 A A C A F19 A A C A F20 A A C C F21A A C C F22 A A C A F23 A A C A F24 A A C A F25 A A C A F26 A A C A F27A A C C F28 A A C C F29 A A C C F30 A A C A F31 A A B A F32 A A C A F33A A C C F34 A A C C F35 A A C C F36 A A C A F37 A A C C F39 A A C C F40A A C C F41 A A C A PF1 A A C B PF2 A A C A PF3 A A C B PF4 A A C B PF8A A C C PF13 A A C C PF31 A A C C

Comparative Data

Bioassays on BAW and CL were conducted according to the proceduresoutlined in Example A: Bioassays on Beet Armyworm (“BAW”) and CabbageLooper (“CL”) using the indicated concentrations. The results areindicated in Table CD1 and Table CD2.

TABLE CD1

5 0.5 0.05 μg/cm² μg/cm² μg/cm² No. R¹⁰ BAW CL BAW CL BAW CL FC1 H   7*100 0 0 0 0 F7 Cl 100 100 100 100 79 100 F4 Br 100 100 100 100 100 100F33 CH₃ 100 100 100 100 88 100 F5 CF₃ 100 100 100 100 100 100 *Percentcontrol (or mortality)

TABLE CD2

5 μg/cm² 0.5 μg/cm² 0.05 μg/cm² No. R¹⁰ BAW CL BAW CL BAW CL FC2 H  100*100 0 6 0 0 F9 Cl 100 100 100 100 100 100 F3 Br 100 100 100 100 100 100F2 CH₃ 100 100 100 100 100 100 F1 CF₃ 100 100 100 100 100 100 *Percentcontrol (or mortality)

1. A molecule having the following formula

wherein: (A) R¹, R⁵, R⁶, R¹¹, R¹², R¹³, and R¹⁴ are each independentlyselected from the group consisting of H, F, Cl, Br, I, CN, (C₁-C₄)alkyl,(C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy; (B) R², R³, andR⁴ are each independently selected from the group consisting of H, F,Cl, Br, I, CN, (C₁-C₄)alkyl, (C₂-C₄)alkenyl, (C₂-C₄)alkynyl,(C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and (C₁-C₄)haloalkoxy; (C) R⁷ is(C₁-C₆)haloalkyl; (D) R⁹ is selected from the group consisting of H, F,Cl, Br, I, CN, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, and(C₁-C₄)haloalkoxy; (E) R¹⁰ is selected from the group consisting of (F),F, Cl, Br, I, CN, (C₁-C₄)alkyl, (C₂-C₄)alkenyl, (C₂-C₄)alkynyl,(C₁-C₄)haloalkyl, C₄)alkoxy, and (C₁-C₄)haloalkoxy; (F) R⁹ and R¹⁰together can optionally form a 3- to 5-membered saturated orunsaturated, hydrocarbyl link, wherein said hydrocarbyl link mayoptionally be substituted with one or more substituents independentlyselected from the group consisting of F, Cl, Br, I, and CN; (G) L is(C₁-C₆)alkyl; (H) X is selected from the group consisting of C, S, andP(C₁-C₆)alkyl; (I) n is 1 or 2; (J) R¹⁵ is selected from the groupconsisting of (C₁-C₄)alkyl, (C₂-C₄)alkenyl, (C₃-C₄)cycloalkyl,(C₁-C₄)haloalkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkoxy, phenyl, andNH(C₃-C₄)cycloalkyl, wherein each alkyl, alkenyl, cycloalkyl, haloalkyl,alkoxy, haloalkoxy, and phenyl may optionally be substituted with one ormore substituents independently selected from the group consisting of F,Cl, Br, I, CN, and OH; and agriculturally acceptable acid additionsalts, salt derivatives, solvates, ester derivatives, crystalpolymorphs, isotopes, resolved stereoisomers, and tautomers, of themolecules of Formula One.
 2. A molecule according to claim 1 wherein R¹,R³, R⁴, R⁵, R⁶, R⁹, R¹¹, R¹², R¹³, and R¹⁴ are H.
 3. A moleculeaccording to claim 1 wherein R² is Cl, Br, or CH₃.
 4. A moleculeaccording to claim 1 wherein R³ is F, Cl, Br, or CH═CH₂.
 5. A moleculeaccording to claim 1 wherein R⁴ is Cl, Br, or CH₃.
 6. A moleculeaccording to claim 1 wherein R², R³, and R⁴ are Cl.
 7. A moleculeaccording to claim 1 wherein R⁷ is (C₁-C₆)haloalkyl.
 8. A moleculeaccording to claim 1 wherein R⁷ is CF₃, CF₂CH₃, or CF₂CH₂CH₃.
 9. Amolecule according to claim 1 wherein R¹⁰ is Cl, Br, I, CH₃, or CF₃. 10.A molecule according to claim 1 wherein L is CH(CH₃) or CH(CH₂CH₃). 11.A molecule according to claim 1 wherein X is C or S.
 12. A moleculeaccording to claim 1 wherein n is 1 or
 2. 13. A molecule according toclaim 1 wherein R¹⁵ is CH₂CH₃, cyclopropyl, CH₂CF₃, CH₂CH₂CF₃, orNHcyclopropyl.
 14. A molecule according to claim 1 wherein (A) R¹, R⁵,R⁶, R¹¹, R¹², R¹³, and R¹⁴ are H; (B) R², R³, and R⁴ are eachindependently selected from the group consisting of H, F, Cl, Br,(C₁-C₄)alkyl, (C₂-C₄)alkenyl; (C) R⁷ is (C₁-C₆)haloalkyl; (D) R⁹ is H;(E) R¹⁰ is selected from the group consisting of Cl, Br, (C₁-C₄)alkyl,and (C₁-C₄)haloalkyl; (G) L is (C₁-C₆)alkyl; (H) X is C or S; (I) n is 1or 2; (J) R¹⁵ is selected from the group consisting of (C₁-C₄)alkyl,(C₃-C₄)cycloalkyl, (C₁-C₄)haloalkyl, and NH(C₃-C₄)cycloalkyl, whereineach alkyl, alkenyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, andphenyl may optionally be substituted with one or more substituentsindependently selected from the group consisting of F, Cl, Br, I, CN,and OH.
 15. A molecule according to claim 1 wherein said molecule isselected from one of the molecules in Table
 2. 16. A molecule accordingto claim 1 wherein said molecule is selected from one of the moleculesin Table
 1. 17. A pesticidal composition comprising a molecule accordingto claim 1 further comprising one or more active ingredients.
 18. Apesticidal composition according to claim 17 wherein said activeingredient is from AIGA.
 19. A process to control a pest said processcomprising applying to a locus, a pesticidally effective amount of apesticidal composition wherein said pesticidal composition comprises amolecule according to claim
 1. 20. A process comprising applying amolecule according to 1 to a locus that includes a non-human animal tocontrol endoparasites and/or ectoparasites.